The 5th Annual

NC State University

Undergraduate Summer Research Symposium

 

NSF Alliances for Graduate Education

and the Professoriate (AGEP) SRE

 


Abstracts are listed in alphabetical order by the last name of the corresponding author.

 


 

 

Student Author(s): 

Arribas, Ricardo L.

Petzold, Jennifer

Home Institution:

University of Puerto Rico- Cayey

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biological Sciences

Research Mentor(s)

Fred Gould/Entomology

Title of Presentation:

Physical Responses of Physalis Leaves to H. sublexa Eggs

 

Plant- insect interactions include many different types of relationships, some of which are negative for the plant. Plants have evolved defenses against many different threats; one of these defenses is the formation of undifferentiated cells where insects oviposit on the leaf. This kind of response can be observed in Physalis plants when H. sublexa moths lay eggs on the plant. Reaction to H. subflexa eggs on the surface of Physalis leaves may be a defense response specific to this herbivore, and it may result in a decrease in the percent of eggs that hatch. The purpose of this study was to 1) characterize the reactions on Physalis leaves caused by H. sublexa oviposition, 2) determine if percent hatch is affected for eggs under which the plant has reacted versus eggs lacking a plant response, and 3) determine if this reaction is specific to H. sublexa or if the plant reacts to other Lepidopteran insect oviposition. Reactions to eggs were characterized for three Physalis species--P. pubescens, P. angulata, and P. cordata. The responses were identified as two types: a) a discoloration of the leaf directly under the egg, forming a yellow circular patch that increased in diameter over time and eventually resulted in tissue death, and b) a proliferation of cells in the shape of a volcano under the egg, varying in size. Preliminary results revealed that 44% of eggs to which the plant reacted hatched, while only 29% of the eggs with no plant reaction hatched, meaning that a reaction by the plant may not affect the eggs in a negative way. It is possible that the Physalis plant is reacting to oviposition with the purpose of pushing the egg off the plant to prevent feeding damage, or to make it easier for predators to attack the egg.

 


 

 

Student Author(s): 

Barr, Amy M.

Patel, Mukund

Home Institution:

Troy University

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biological and Environmental Sciences

Genetics

Research Mentor(s)

James W. Mahaffey/Genetics

Title of Presentation:

Identification and Characterization of Protein Interactions with the Drosophila Disconnected (disco) Gene

 

 

Most animals have a segmented body, with morphological distinctions in the segments along the anterior/posterior body axis. These differences are established during development by differential  expression of the Hox homeodomain transcription factors along the body axis. The different Hox proteins activate different sets of target genes, thus creating each unique body segment (for example, head, trunk, and abdomen). However, it is clear from many studies that the Hox proteins do not work alone; specific cofactors are needed. The Drosophila gene disconnected (disco) may encode one such cofactor that functions with the head Hox proteins. disco is required for proper larval head development, and in embryos lacking disco the head segments develop as if they have lost Hox input. Gene regulation is a very complex process, and even Disco does not function alone. The objective of my study was to identify other factors that interact with Disco. I employed a yeast two hybrid assay to identify genes encoding potential Disco interactors. My initial screen identified 21 clones encoding proteins that were positive for an interaction. I am now in the process of characterizing these clones to determine the identity of each gene. Once the genes are identified, I will begin to address how the encoded proteins participate with Disco and the Hox proteins to establish segment identities during Drosophila development. Since the Hox proteins and Disco are conserved in all metazoans, understanding how these factors contribute to development of Drosophila will contribute to our knowledge of development in all animals. 

 


 

 

Student Author(s): 

Belton, Jon-Matthew

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biochemistry

Research Mentor(s)

Linda Haley-Bowdoin/Biochemistry

Title of Presentation:

Immunolocalization of AL1, Geminivirus Replication Factor, in Arabidopsis  Plants Infected with Cabbage Leaf Curl Virus

 

Cabbage Leaf Curl Virus (CaLCuV) is a member of the Geminiviridae family of plant viruses. Geminiviruses cause agricultural epidemics world wide, devastating a variety of crops including cassava, tomato, cotton and maize.  Geminiviruses are characterized by their small, circular, single-stranded DNA genomes with either one or two chromosomes and by their double icosohedral viral particles. We used immunolocalization assays to study the viral replication protein, AL1, in wild type and mutant lines of Arabidopsis thaliana Col-0.  Plants were inoculated with Agrobacterium tumefaciens carrying T-DNA constructs with the A and B genomes of CaLCuV. Microscopic analysis of vibratome-generated sections of infected plant tissues revealed the relative concentrations of virus in specific tissues. This information adds to our understanding of the infection process in the Arabidopsis model system.

 


 

 

Student Author(s): 

Blue, Aaron W.

He, Peng

Home Institution:

Fayetteville State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Chemistry

Research Mentor(s)

Lin He/Chemistry

Title of Presentation:

Amplification-by-Polymerization in Fluorescence-based DNA Sensing

 

 

The aim of this work is to incorporate fluorophores on polymer brushes to enhance DNA detection on a surface-initiated Atom Transfer Radical Polymerization (ATRP) reaction for fluorescence measurements. It has been previously discussed that under optimized ATRP reaction conditions, that the direct visualization of poly (2-hydroxyethyl methacrylate) PHEMA growth can be observed when running longer reaction times1. It has also been noted for any DNA-sensing application faster reaction times are desired1.  Incorporating fluorophores onto polymer brushes has the potential of improving DNA detection sensitivity and shortening the assay time.  In the concept-proof experiment, ATRP initiator-coupled ssDNA molecules were immobilized on a gold surface.  ATRP polymerization was then carried out and the amount of PHEMA formed was measured using ellipsometry. Carbonyldiimidazole (CDI) was used to react with the hydroxyl groups of the polymer, allowing the attachment of the flourophores (5-(6)-((N-(5-aminopentyl)amino)carbonyl)tetramethylrhodamine).  The successful incorporation of the fluorescent dyes to the polymers was examined using a fluorescence microscope.  The selection of the proper fluorescent dyes and coupling conditions were also conducted.  The preliminary data show that the incorporation of fluorescence detection could be used to improve the performance of polymer-assisted DNA Sensing.

 

 


 

 

Student Author(s): 

Caldwell, Ticola S.

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Psychology

Research Mentor(s)

Pamela Martin/Psychology

Title of Presentation:

Factors that Contribute or Hinder Achievement Motivation among Low-income African American Elementary Students

 

 

The focus of this qualitative study is to examine the multiple factors that influence the reasons why low-income African American elementary age students are experiencing low academic achievement. Four educators in the North Carolina area were interviewed about their opinions and theories of academic motivation in relation to low-income African American students.  A content analysis was employed to determine the underlying themes discussed by the participants.  The themes underscore the importance of children nested in the context of their family, school, and community to understand the diverse learning strategies children bring to school, especially, low-income African American students.  This research underscores the role of parental socialization as well as extended family networks in communicating values about African American culture and education. Implications for future community and school based interventions are also discussed.  

 


 

 

Student Author(s): 

Caro, Eduardo J.E.

Home Institution:

University of Puerto Rico Rio Piedras

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Chemistry

Research Mentor(s)

Christopher B. Gorman/Chemistry

Title of Presentation:

Effective Synthetic Route to Indanols

 

 

 

Indanols are important synthetic intermediates both in pharmaceutical applications and in emerging polymerization routes under development in the Gorman Group at NCSU.  An effective synthetic route was devised to produce substituted indanols. The synthetic scheme consists of three steps, using 3,5-dibromobenzaldehyde as starting material. Structure characterization of each product was obtained through ¹H-NMR.

 

 


 

 

Student Author(s): 

Cepero, Keren J.

Home Institution:

UPR Rio Piedras

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Forestry Department of Natural Resources

Research Mentor(s)

Stacy A.C. Nelson/Forestry Department of Natural Resources

Title of Presentation:

Microclimate and Water Quality of Black Creek Watershed

 

 

 

Urban streams are faced with constant pressures from surrounding land uses. Development within the urban environment contributes to a series of anthropogenic stressors. These stressors within the aquatic environment including excess sedimentation nutrients and chemicals may also be amplified by microclimatic conditions within local areas. The objective of this study was to examine the effect of land use stressors and water quality and short range microclimate conditions (air temperature, precipitation, barometric pressure) with in the Black Creek Watershed at Cary, NC. Water quality samples were collected insitu and analyze with a La Motte Smart Spectro Spectrophotometer. Land use and water quality relationships were examine using GIS and used to compare short range microclimate conditions. Understanding these relationships will allow for improved management of local watershed.

 

 


 

 

 

Student Author(s): 

Edathil, Roshen T.

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Structural and Molecular Biochemistry

Research Mentor(s)

William L. Miller/Biochemistry

Title of Presentation:

Identification of Transcription Factors that Partner with Smad3/4 to Induce Transcription of  FSH-beta

 

 

Follicle Stimulating Hormone (FSH) is required for  egg and sperm production in mammals.  FSH is an alpha/beta  heterodimer with FSH-beta controlling overall expression. Because of its importance, FSH-beta is controlled by more than 6 hormones, one of which is activin-A, a transforming growth factor beta (TGF-beta) family member.  Activin typically activates Smad3, a nuclear transcription factor, that then binds Smad4 and other transcription factors to form DNA-enhancesome promoter complexes to induce gene transcription.  One Smad binding site in the FSH-beta promoter seems especially important for FSH expression  (-166GTTTAGAC-159).  My goal this summer has been to isolate the nuclear transcription complex containing Smad3/4 and all other proteins involved in inducing FSH-beta transcription.  I increased Smad3 concentrations in FSH-producing cells (LbetaT2) by transient transfection of a Smad3 expression plasmid, isolated the nuclear proteins and incubated the nuclear extract with biotinylated DNA known to bind Smad3/4 most efficiently (GTCTAGAC-biotin).  The  DNA-Smad3/4-enhancesome complex was isolated using streptavidin-coated magnetic microbeads that were captured on a magnetic column.   Western blotting with antibodies was used to show efficient extraction of Smad3/4 (chemiluminescence).  Other proteins in the complex will be identified using HPLC-Mass Spectral analysis.  Optimization of this technique using Smad3/4 was necessary to ensure efficient extraction of enhancesome proteins.  Characterization of the Smad-associated transcription factors on the  FSHâ promoter will identify proteins that can partner with Smad3/4 and may be important in hundreds of other activin-induced promoters.

 

 

 


 

 

Student Author(s): 

Fairey, Donta' J

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Center for Earth Observation Forestry and Environmental Resources

Research Mentor(s)

Justin M. Shedd/Forestry and Environmental Resources

Stacy A. C.  Nelson/Forestry and Environmental Resources

Title of Presentation:

Development of GIS Techniques for Effective Wetland Delineations

 

 

 

The Blue Ridge Parkway, stretching 469 miles between Virginia and North Carolina, connects the great Smokey Mountains and the Shenandoah National park. This park unit is part of the U.S. National Park Service’s National Park System. Federal regulations require zero impacts on wetland systems within park lands. However, effective determinations of wetland boundaries are limited by regulatory agency budgetary constraints, labor and time. The objective of this study includes using widely available spatial information and GIS tools to determine and verify wetland boundaries within the Blue Ridge Parkway unit. Methods developed in this study will facilitate State and Federal regulatory agencies in time and cost-effective wetland inventories over large areas such as the Blue Ridge Parkway.

 


 

 

Student Author(s): 

Gonzalez, Jessica

Home Institution:

University of Puerto Rico, Rio Piedras

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Chemistry

Research Mentor(s)

David A. Shultz/Chemistry

Title of Presentation:

A Comparison of the Valence Tautomeric Behavior between (4-X-pyridine) 2Co(diox) 2 Complexes and (4,4’-di-X-2,2’-bipyridine)Co(diox) 2 Complexes Using Variable Temperature Infrared Spectroscopy

 

 

A study of the intramolecular cobalt-quinone electron transfer has been carried out in a series of complexes of general formula (4-X-pyridine) 2Co(diox) 2 and (4,4’-di-X-2,2’-bipyridine)Co(diox) 2 where “diox” is 3,5-di-tert-butyl-o-benzosemiquinone/3,5-di-tert-butyl-o-catecholate and X is -H, -NO2 and -Br.  The (4-X-pyridine) 2Co(diox) 2 complexes and  (4,4’-di-X-2,2’-bipyridine)Co(diox) 2 complexes were synthesized and their magnetic properties were analyzed with a Superconducting QUantum Interference Device (SQUID) magnetometer, while characteristic optical transitions were probed using Variable Temperature Infrared Spectroscopy (VTIR) to support the electron transfer between the metal ion and one of the quinone ligands.  The optical absorptions that appear in the 3700nm region of the infrared for the Co(III) complexes are assigned to Cat - SQ charge transfer transitions.  As the temperature was varied, spectral changes were  observed on this region.  This fact suggests a thermally-driven valence tautomeric interconversion between Co(II) species and the Co(III) form in (4,4’-di-X-2,2’-bipyridine)Co(diox) 2 complexes.  While in (4-X-pyridine)2Co(diox) 2 complexes, the spectral  changes were not observed, suggesting that the equilibrium may not occur.  A mechanism for the differences in valence tautomeric behavior for  these complexes is offered. 

 

 


 

 

Student Author(s): 

Hagan, Diane

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Textile and Apparel, Technology and Management

Research Mentor(s)

Traci May/Textile and Apparel, Technology and Management 

Title of Presentation:

Color Variation in Digital Textile Printing: Influence of Fiber Content and Other Substrate Characteristics

 

 

The purpose of this research is to study variations in colors that are digitally printed on textile substrates composed of different fibers, identify major and minor factors that contribute to these variations, and seek ways to control these variations.

Nine fabrics that differed in weave structure, fiber composition, and/or preprinted color were characterized according to  molecular structure, physical properties, and pre-printed color (after pretreatment). Based on previous research, these substrate properties were expected to influence the resulting color in the printed fabric. A multicolor design was printed on all of the fabrics with a large format textile printer that used cyan, magenta, yellow, black (CMYK), and turquoise and orange dye-based inks. Because of the dye affinity of the selected fabrics, reactive dye inks, as opposed to acid dye inks, were used for the printing. After fabrics were steamed and washed, coloration differences were assessed by comparing fabrics visually side-by-side in a controlled environment and objectively with a colorimeter.

               The color differences made the relationship between the various fibers and the fixed selection of dyes apparent. The primary factor that affected coloration differences among the fabrics was the molecular  structure of the fiber in the textile substrate, or the fiber content, while the minor factors like the preprinted color and weave structure of the fabric gave only slight variation in the printed color.  Many previous researchers have shown that color management systems (CMS) have been a major way to control the color discrepancies in digital textile printing. This work demonstrates the importance of including fiber content of the substrate as a variable in color management systems.

 


 

 

Student Author(s): 

Ho, Kiti

Han, Sang-oh

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Molecular and Structural Biochemistry

Research Mentor(s)

William L. Miller/Biochemistry

Title of Presentation:

Searching for Activin Responsive Elements (ARE) on the Promoter of Ovine Follicle Stimulating Hormone Beta-subunit

 

 

Ovine follicle stimulating hormone beta-subunit (oFSH beta) is produced by pituitary gonadotropes. It partners with its alpha subunit to regulate the development of sperm and eggs, thus controlling fertility in all vertebrates. One of the hormones that regulates oFSH beta expression is activin. Activin belongs to the transforming growth factor beta super family (TGF-beta), which controls the development of most cells in the body until they become fully differentiated. Regulation of oFSH beta by activin serves as a model for studying activin action on many genes in numerous cell types. It is still not clear, however, how activin stimulates oFSH beta. Studies have discovered one ARE on the oFSH beta promoter, which is between -166 bp and -159 bp, but this element, by itself, is not enough to account for the potent effect of activin. Our goal is to define all ARE sites on the oFSH beta promoter. In order to achieve this goal, we used two approaches. One is by deletion mutagenesis, which deletes promoter sequences and looks for loss of activin action. A side effect of deletion analysis is that certain promoter sequences are brought closer to the transcription starting point, which can falsely alter activin action. The other approach is to replace DNA sequences with spacer DNA. This approach does not change spacing. In this project, I studied the -750/-169 region of the promoter. I found a loss in activin induction when I deleted this element or replaced it with spacer DNA, indicating that ARE site(s) exist(s) within this region.

 

 


 

 

Student Author(s): 

Hume, Samuel

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Electrical and Computer Engineering

Research Mentor(s)

Winser Alexander

William Edmonson

Title of Presentation:

A Comparison of Tools Used to Analyze System Characteristics of Biochemical Models

 

 

The project involved an evaluation of two simulation packages along with the use of the Systems Biology Markup Language (SBML) to describe and analyze biological systems. Identifying a unified way to describe and  analyze biological systems in software is a critical component of system biology research. It is a necessity to have information standards if models are

to be shared, evaluated, and cooperatively developed. Otherwise, a considerable amount of time would be spent translating biochemical reactions models from one representation to another, and valuable  information could be lost in the process.  The Systems Biology Markup Language (SBML) is a free and well-accepted XML-based language for representing and

exchanging models between simulation and analysis tools.  The SBToolBox for MATLAB and the Systems Biology Workbench (SBW) were the simulation packages used in the evaluation. The metrics used for  performing the comparative analysis of the above tools were: steady-state analysis, stability analysis, simulation time, in-silico experiments, bifurcation analysis, parameter estimation, and parameter sensitivity. The goal for the project was to provide information for use to decide which tool is better suited for the analysis of a given model.

 

 


 

 

Student Author(s): 

Kelley, Lauren N.

Home Institution:

Norfolk State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Microbiology

Research Mentor(s)

Hosni M. Hassan/Microbiology

Matthew  R. Evans/Microbiology

Title of Presentation:

The Impact of Varying Concentrations of Paraquat on SOD Activity of Log-Phage Cells of Salmonella enterica Typhimurium ATCC 14028s

 

      

Oxygen toxicity plays an important role in cellular injury as well as in many common diseases, and is controlled by a balance between the rates of generations of reduced oxygen species and the removal of those species. Superoxide dismutases are metalloenzymes that are essential for the defense against oxygen toxicity. Redox cycling compounds such as the herbicide paraquat (PQ), propagate the formation of the superoxide radicals ( .O2 - ).  Superoxide dismutases (SODs) catalyze the dismutation of superoxide radicals ( .O2 - ) to hydrogen peroxide and oxygen. Salmonella enterica Typhimurium is an intracellular pathogen that infects human and causes gastroenteritis. However it causes typhoid-like fever in mice. S. Typhimurium possesses three types of SODs, which are copper and zinc (CuZnSOD), manganese (MnSOD), and iron (FeSOD). The goal of this project was to study the effect of paraquat on growth and synthesis of SODs in logarithmic phase cells of S. Typhimurium. S. Typhimurium was grown in LB-MOPS  medium containing 20mM xylose. Log phase cells were exposed to different concentrations of paraquat (0 .0, 0.3, 0.5, and 1.0mM) starting at an OD600 of 0.3. Aliquots were taken prior to exposure to PQ and every 15 minutes thereafter until 75 minutes had elapsed.  A Bradford assay was performed to determine amount of protein in each sample, the total SOD  activity was determined, and the activity of each type of SOD (Mn, Fe, Cu/Zn hybrid) was visualized using a native protein gel/activity stain.

 

 


 

 

Student Author(s): 

Khan, George

Home Institution:

Norfolk State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Forestry & Environmental Resources

Research Mentor(s)

Ross Whetten/Forestry & Environmental Resources

Title of Presentation:

Pilot study to Investigate Chemically Induced Resistance in Fir Species (Abies spp.) against Phytophthora cinnamomi

 

 

Phytophthora root rot and stem canker is one of the most important diseases of Abies species that are grown as Christmas trees. For example, root rot, caused by Phytophthora cinnamomi is a serious problem on Fraser fir in nurseries and Christmas tree plantations in western North Carolina. North Carolina will experience an average industry-wide loss from Phytophthora root rot of about $9 million based on a $100 million industry. Phytophthora root rot is caused by the oomycete P. cinnamomi Rand. This study looks at the effect of pre-treating seedlings with a chemical known to induce disease resistance in plants. Effects of treatment will be measured at the level of disease incidence, and at the level of gene expression. Two species of fir will be used for this experiment: a fully susceptible species, Abies fraseri, and a resistant species, Abies firma. One to three month old seedlings will be pretreated with Fosphite, then inoculated with zoospores from P. cinnamomi. We will compare the different plants and treatments levels for any changes or resistance triggered when exposed to this chemical.

 

 


 

 

Student Author(s): 

Lawrence, Charlie  III

Morris, Eric B.

Home Institution:

Fayetteville State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Forestry & Environmental Resources

Research Mentor(s)

Glenn P. Catts/Forestry and Environmental Resources

Title of Presentation:

Application of  Spatial Technology to the Field Assessment of Soil compaction Resulting from Equestrian Activity

 

Excessive soil compaction can negatively influence soil productivity and water quality for long periods of time. Horse traffic on forest trails causes soil compaction. Soil compaction is recognized as a field  indicator of sustainable forest management.

               Horseback riding is a recreational activity that occurs with regularity on Hill Forest. Hill Forest managers want some estimate of the impacts from equestrian activities. Mapping trail locations and assessing trail compaction status is facilitated by modern spatial technologies like global positioning systems (GPS) and geographic information systems (GIS) implemented on handheld computing devices.

               We applied cost efficient spatial technology to map and assess the compaction suffered on horse trails on the Hill Forest located in northern Durham County, North Carolina. The location of the horse trails of interest were provided by the Hill Forest management staff as hard copy maps and then converted into GIS files that were used in sampling design and handheld field navigation.

               Variables describing elevation, slope, soil type, distance to hard surface roads and perennial streams were extracted from public domain GIS data and used to select locations for field sampling. Field sampling was accomplished using custom-configured data entry forms at selected locations while taking penetrometer readings of soil compaction in transects perpendicular to the direction of and across selected  horse trails. Subsequent analysis compares the degree of compaction measured by the penetrometer as a function of one or more of the field-collected or GIS-based variables.

               At the request of the Hill Forest management staff, field photographs were also acquired and spatially referenced using time and date synchronization with GPS records collected on the hand held computer. Field photos of trail conditions can be recalled by mouse-clicking on locations in a desktop GIS map depicting field data collection efforts.

 

 


 

 

Student Author(s): 

Lopez, Harry O.

Kirst, Mariana E.

Holmes, Robert A.

Home Institution:

University of Puerto Rico at Cayey

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biology

Plant Biology

Research Mentor(s)

Rebecca S. Boston/Plant Biology

Title of Presentation:

Production of Recombinant Maize Ubiquitin Conjugating Enzymes in  E. coli

 

 

The endoplasmic reticulum (ER) is an organelle formed from a network of membranous tubules equipped with molecular chaperones and enzymes essential to protein folding. Correctly folded proteins are exported from the endoplasmic reticulum, while misfolded proteins are retained and selectively degraded by a process known as ER-associated degradation (ERAD). We used bioinformatic tools to identify putative maize homologs of several proteins implicated in ERAD processes in other organisms.  Ubiquitin conjugating enzymes (Ubc1p & Ubc6p) are cytosolic proteins that mediate targeting of short-lived and abnormal proteins for degradation. Hydroxymethyglutaryl reductase degradation protein (Hrd1) is an ER membrane protein that facilitates proper degradation of misfolded membrane proteins. Our goal was to produce recombinant maize Ubc1p, Ubc6p and Hrd1 proteins in an IPTG-inducible E. coli expression system for antibody production and protein interaction studies. We used a pRSET plasmid vector to produce a fusion protein with polyhistidine and Xpress® epitope tags in-frame with the maize protein coding sequences. Recombinant protein production was assayed under different growth temperatures, induction times, nutrient media and +/- ethanol. Protein solubility was determined by extracting protein under conditions that allow for separation of soluble protein and inclusion bodies. For detection of recombinant proteins, we used a combination of western blotting and general protein staining of SDS-polyacrylamide gels. For soluble Ubc6p a large-scale production and purification yielded 2.45 mg/L.

 

 


 

Student Author(s): 

McLean, Roshaunda L.

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Psychology

Research Mentor(s)

Rebecca Stelter/Psychology

Amy Halberstadt/Psychology

Title of Presentation:

The Relationship between Socio-economic Status and Stress in African-American Parental Emotional Availability

 

 

Previous research suggests that parents’ emotional availability can influence children’s emotion-related behaviors, but how parents develop this emotional availability is not yet known. Thus, the goal of this study is to explore the distal factors that might influence parents’ willingness to actively participate in a conflict discussion. I hypothesized that factors such as stress and socio-economic level are predictors of parental emotional availability (e.g., providing support, requesting and providing information, acknowledging child’s feelings, and going along with the other). The more stressed and the lower the SES of the parent, the less engaged or emotionally available a parent will be in discussions with their child.  A subset of the full sample of African-American parents and children filled out questionnaires and participated in a videotaped problem-solving discussion about one or more current conflicts that they experience with each other. The standard measure for stress is the Daily Inventory of Stressful Events (DISE), which requests parents to recall specific types of stress they experienced in the last 24 hours. SES was measured based on income and educational indices. Emotional availability was globally coded from seven minutes of the parent-child conflict discussion, using a Likert-type scale. Results and implications of findings will be discussed.

 


 

 

Student Author(s): 

Moses, Lorra S.

Home Institution:

Fayetteville State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Molecular and Structural Biochemistry

Research Mentor(s)

Carla Mattos/ Molecular and Structural

Biochemistry

Title of Presentation:

Purification of Raf-RBD-CRD for Crystallization

 

 

Raf is a downstream effector protein of Ras in the growth Mitogen-Activated Protein (MAP) Kinase pathway.  It is a large protein of about 648 amino acids and contains several domains.  Two of the domains bind directly to Ras.  These domains are the Raf- Ras Binding Domain (Raf-RBD) and the Raf-Cysteine Rich Domain (Raf-CRD).  There are published structures of Raf-RBD alone and of  Raf-CRD alone, but there are no structures of the two domains together or of the two domains bound to Ras.  Therefore the main purpose of this research is to purify the protein Raf-RBD-CRD to be crystallized and to crystallize Raf –RBD-CRD bound to Ras making a complex.   Raf  amino acids 1-186 were cloned into the GEV2 vector which was transformed into the E. coli cell line (BL21[DE3]) for expression of the Raf protein.  The E. coli cells were grown in LB media containing ampicillin and allowed to over express the Raf protein.  The Raf protein was expressed with a!  HIS-tag in order to purify it by nickel affinity chromatography. Further  purification was preformed using anion exchange and gel filtration chromatography. SDS Page indicates that purification needs optimizing in order to remove impurities still present.  The future direction of this project is to continue to purify and crystallize Raf to solve the structures by X-ray crystallography.

 


 

 

Student Author(s): 

Munilla, Samuel R.

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Computer Science

Research Mentor(s)

R. Michael Young/Computer Science

Title of Presentation:

Zocalo, an Integrated Planning Framework for Use in Diverse Environments

 

 

Narrative plays a critical role in the way we communicate, learn and interact with one another. Computer systems that take advantage of this natural inclination towards narrative can present information to the user in a much more cohesive and engaging  manner than is possible using conventional methods.  To this end, the Zocalo Project integrates a set of planning agents that work together to fulfill a set of goals inside a virtual environment, while still  presenting an organized narrative to the user.  The three primary components of the Zocalo framework are: Fletcher, a web service that utilizes Crossbow, a partial-order planner based on the DPOCL (Decompositional Partial Order Causal Link) algorithm; Crosswind, a web service that provides Reactive Mediation by creating and maintaining Policy Tress; and Kyudo, a web service that provides Proactive Mediation.  Communication with  this framework is handled by an Execution Manager, which acts as a bridge between the framework and the 3d Engine that renders the virtual world.  In order to demonstrate the capabilities of this framework, an interactive environment was created using Epic’s Unreal2 engine.  This environment presents the user with a single end-goal and allows the user to move about the environment freely.  In the background, the Zocalo framework works to present the user with opportunities that will allow him or her to reach that goal.

 

 


 

 

Student Author(s): 

Muñoz, Jessian L.

Gore, Jesse A.

Home Institution:

University of Puerto Rico at Cayey

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biochemistry

Research Mentor(s)

William L. Miller/Biochemistry

Title of Presentation:

Gonadotropin Releasing Hormone Inhibits

Activin-Induced Transcription Complexes

on the Ovine Follicle Stimulating Hormone Beta

Promoter

 

 

Follicle Stimulating Hormone (FSH) is an alpha/beta heterodimeric glycoprotein which is required for  reproductive function of all vertebrates. Activin plays a major role in the production of FSH as it induces FSH beta production. Gonadotropin releasing hormone (GnRH) is a decapeptide produced in the hypothalamus, which induces FSH beta expression through a MAP kinase pathway.  Induction requires pulsatile GnRH release (5 min each hour). Our laboratory has shown, however, that when gonadotropes are treated with GnRH at high, chronic levels, GnRH can inhibit activin-induced FSH beta expression, perhaps, through a cAMP/CREB pathway.  I used electrophoretic mobility shift assays (EMSAs) to determine if GnRH treatment could disrupt FSH beta promoter complexes known to be important for FSH beta induction by activin. LbetaT2 cells were treated with  activin ± GnRH and their nuclear proteins were then incubated with SMAD3/4 binding sites. These are DNA sequences on the FSH beta  promoter known to bind SMADs which are proteins induced by activin. I found that these SMAD3/4:DNA complexes were,  indeed, disrupted by GnRH. Through our experimentation, we were able to show that GnRH inhibits a key transcriptional complex needed for activin induction of oFSH beta transcription. This is the first example of a hormone being able to block activin induction at a transcriptional level.

 

 

 


 

 

Student Author(s): 

O'Neal, Zeltina D.

Home Institution:

North Carolina Central University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biology

Research Mentor(s)

Amy M. Grunden/Microbiology

Title of Presentation:

Expression and Biochemical

Characterization of Pyrococcus furiosus Prolidase Homolog-2 for Potential Use in

Organophosphorus Nerve Agent Detoxification

 

 

Study of prolidase enzymes isolated from the hyperthermophilic archaeon Pyrococcus furiosus for use as potential detoxification agents against toxic organophosphorus (OP) compounds has been ongoing.  It has been shown that prolidases can hydrolyze the characteristic P-F and P-O bonds found in the toxic nerve agents soman and sarin.  The P. furiosus prolidase is an attractive candidate enzyme for OP agent detoxification because it is extremely thermostable.  However, even though P. furiosus prolidase can withstand higher temperatures, it has some disadvantages.  It requires the addition of the metal ion Co2+ for activity and has little activity below 50°C.  For these reasons, other enzymes with homology to P. furiosus prolidase are being studied as alternate decontamination agents.  Recently a prolidase homolog was identified in the P. furiosus genome, prolidase homolog 2, which has 43% similarity to the previously characterize P. furiosus prolidase.  For this study, the P. furiosus prolidase homolog 2 was cloned into the T7 RNA polymerase-base expression vector pET-21b.  The recombinant P. furiosus prolidase homolog 2 protein was over-expressed in Escherichia coli strain BL21(λDE3) using both LB and autoinduction media.  Experiments were conducted to demonstrate the thermostability  of recombinant P. furiosus prolidase homolog 2 and evaluate its substrate and metal preference.

 

 

 


 

 

Student Author(s): 

Onori, John E.

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Polymer and Color Chemistry

Research Mentor(s)

Richard Kotek/Polymer and Color Chemistry

Title of Presentation:

Viscosity Measurements of Cellulose in ED/KSCN Salt System

 

 

Cellulose is a natural polymer which is found in trees and plants and is commonly used for making milk and juice cartons. The problem with cellulose is that it does not melt and dissolve in the common solvents. Cuen (copper-Ethylenediamine complex) solution is the only solvent used for viscosity measurements of cellulose. The objective of this experiment is to take a similar solvent like  potassium Thiocyanate Ethylenediamine system, dissolve different types of cellulose  and take viscosity measurements to find there intrinsic viscosities. Each cellulose sample was ground up, dried in a vacuum oven over night and measured on an analytical balance. 50 ml glass reactor equipped with a mechanical stirrer was used for dissolution. Ethylenediamine and potassium Thiocyanate were added in first to create the solvent, and then the cellulose sample was added in, it took about 24-48 hours for the complete cellulose dissolution. An Ubbelohde viscometer, the constant temperature bath (held at 25oC) and a stop watch was used to determine the flow times of each solution. Intrinsic viscosity was calculated using a series of equations that included relative, specific, reduced, and inherent viscosities.  Intrinsic viscosity was found by plotting reduced and inherent viscosity vs. cellulose concentration and extrapolating reduced and inherent viscosity back to the zero concentration. These two viscosities should meet at the same point. We were successful in finding the intrinsic viscosity of AV CELL and Tycell.  Both Inherent and reduced viscosity agreed with each other.  Future work will be to use their intrinsic viscosity to help determine the molecular weight and Degree of polymerization of AV Cell and Tycell.

 


 

 

Student Author(s): 

Otero, Ariel O.

Ondachi, Pauline W.

Home Institution:

University of Puerto Rico at Cayey

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Chemistry

Research Mentor(s)

Daniel L. Comins/Chemistry

Title of Presentation:

Regioselective Substitution of (S)-Nicotine and Nicotine Derivatives

 

 

A variety of novel nicotine derivatives were prepared starting from natural (S)-nicotine. Several functional groups were introduced onto the pyridine ring of nicotine via a regioselective deprotonation and substitution of the C-2, C-4 and C-6 positions. The pharmacological effects of these derivatives on the central nervous system (CNS) and their potential for cancer treatment will be examined.                 

 

 

 


 

 

Student Author(s): 

Park, Ji-Seon

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biochemistry

Research Mentor(s)

Robert B. Rose/Biochemistry

Title of Presentation:

The Use of DCoH/HNF-1 fusion Protein as a Tool to Analyze the Activities of a Bifunctional Protein DCoH

 

DCoH (dimerization cofactor of HNF-1) is a bifunctional protein which functions as a metabolic enzyme in the cytoplasm and a transcriptional coactivator in the nucleus. In the nucleus, DCoH interacts with the transcription factor HNF-1alpha (hepatocyte nuclear factor-1-alpha) and stabilizes HNF-1alpha dimers. Significantly, mutations in HNF-1-alpha are the most common cause of Maturity-onset diabetes of the young (MODY). We have generated a DCoH/HNF-1 fusion protein to determine: 1) whether the two functions of DCoH are independent and 2) how DCoH increases the transcriptional activity of HNF-1. The DCoH and HNF-1 coding sequences were linked by Polymerase Chain Reaction (PCR) using a primer overlap strategy and ligated into a mammalian _expression vector. The DCoH/HNF-1 fusion protein will be tested for enzymatic activity to determine whether formation of the interaction with HNF-1 might regulate the enzymatic activity of DCoH. One study has concluded that DCoH does not lose its enzymatic activity when it is bound to HNF-1. However, this study did not determine whether the DCoH/HNF-1 complex was stable throughout the study. Structural studies of the DCoH/HNF-1-alpha complex indicate an active site residue of DCoH is involved in interaction with HNF-1, suggesting the DCoH/HNF-1 complex should be enzymatically inactive. The fusion protein will prevent dissociation of the complex during the enzyme assay. The fusion protein will also allow us to determine how DCoH increases the transcriptional activity of HNF-1. Our current hypothesis is that DCoH increases the half-life of HNF-1.

 

 


 

 

Student Author(s): 

Plaza, Tomas E.

Home Institution:

Metropolitan University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Developmental Psychology

Research Mentor(s)

Jason C. Allaire/Developmental Psychology

Title of Presentation:

Examining Health as a Mediator of the Relationship between Education and Cognitio

 

 

Previous studies have found a strong relationship between education and memory.  In addition, health factors such as physical functioning and mental health have been shown to be related to education and memory.  Consequently, the aim of this study is to determine whether health mediates the relationship between education and memory performance.  It is expected that health factors will explain differences in memory performance once attributed to demographic factors. The sample consisted of 107 urban living African American elders with a mean age of 71 years (SD = 10.01; range = 52 – 94 years).  During testing participants were given a multifaceted battery, which assessed years and quality of education, working memory, and subjective health assessments.  Results indicated that years of education and the self-reported quality of education were associated with working memory as was self-reported health.  Regression analyses revealed that the effect of education on working memory performance was only partially mediated by health. Discussion will focus on the importance of assessing quality of education and its’ association with health and memory. 

 

 

 


 

 

Student Author(s): 

Powell, Amanda M.

Home Institution:

Shaw University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Zoology

Research Mentor(s)

Brenda J. Grubb/Zoology

Title of Presentation:

Analysis of the Effect of Estrogen on Claudin Tight Junction Proteins

 

 

                 

Estrogen plays a vital role in cell differentiation during mammary tissue development. To understand the basic mechanism of estrogen during development, Xenopus frog embryos were exposed to estrogen and an estrogen inhibitor at a critical stage of sensitivity. The embryos were then fixed, embedded and sectioned for analysis of the effect of estrogen on morphogenesis. An E.L.I.S.A was done to  test for claudin 4, 5 and 7 protein level changes. Claudin levels were also monitored in mouse mammary tissue using histology. Both tumor and normal mammary tissue was observed for the presence of lack of the  proteins. Claudins are a family of tight junction proteins necessary for cell to cell interaction and adhesion. It has been shown that low levels of certain claudins result in metastasis and tumorogenesis. Loss of claudin results in reduced cell adhesion, allowing cells to break away and metastasize. We are trying to monitor the effects of estrogen on claudin levels.  It is hypothesized that there is a direct correlation between estrogenic affects on morphogenesis and altered claudin levels.

 

 

 


 

 

Student Author(s): 

Ramirez Vicens, Magaly A.

Munro-Leighton, Colleen

Delp, Samuel A.

Home Institution:

University of Puerto Rico at Cayey

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Chemistry

Research Mentor(s)

T. Brent Gunnoe/Chemistry

Title of Presentation:

Catalytic C-S Bond Formation by Monomeric Copper(I) Sulfido Complexes

 

 

 

Natural products and biologically active compounds often contain C-X (X = O, N or S) bonds. Thus the development of new catalysts for C-X bond formation is an important pursuit, including routes for C-S bond formation. The monomeric Cu(I) complexes  (IPr)Cu(Y), (IMes)Cu(Y) and (SIPr)Cu(Y) (Y = SPh, SCH2Ph; IPr, IMes, SIPr = N-heterocyclic carbenes) have been prepared, and these complexes serve as catalysts for the addition of S-H bonds across double bonds of electron-deficient olefins. Among transition metals, copper is attractive as a catalyst because of its low expense. The reactivity of these complexes extends to a variety of olefins including acrylonitrile, methyl vinyl ketone, methyl acrylate and cyclohexenone.

 

 


 

 

Student Author(s): 

Rivera, Ivelisse

Stelter, Rebecca

Home Institution:

Universidad Metropolitana

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Psychology

Research Mentor(s)

Amy Halberstadt /Psychology

Title of Presentation:

Exploring Relationships: Parent's Beliefs about Children’s Emotions and Emotional Availability

 

   

Parents' emotional availability may be an important component of children's socioemotional lives.This study will examine how parents' beliefs about emotion may relate to emotional availability with their children. African American parents and their 9- to 10- year old child participated. Parents filled out the PBACE, a questionnaire with five subscales about parents' beliefs about the value, danger and controllability of emotion. Children filled out the LEAP, a questionnaire about the children's perceptions of their parents' emotion availability. Predictions are that parents' valuing  of emotion will be associated with their children's assessing them as emotionally available. Whereas parent's belief that emotion is somewhat dangerous will be associated with children perceiving parents as rather distant. Results are forthcoming.


 

 

Student Author(s): 

Santiago, Lisandra

D'Antonio, Edward L.

Home Institution:

University of Puerto Rico at Cayey

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Chemistry

Research Mentor(s)

Edmond F. Bowden/Chemistry

Title of Presentation:

Diffusionless  Electrochemistry of   Dehaloperoxidase Electrostatically Adsorbed to Alkanethiol Self-Assembled  Monolayers

 

              

Dehaloperoxidase (DHP) is a heme enzyme isolated from the marine worm Amphitrite ornata that has the ability to dehalogenate trihalogenated phenols.  These toxic aromatic contaminants present a major environmental concern, especially to aquatic organisms that cannot metabolize haloaromatics.  DHP in the presence of peroxide can convert these halophenols into environmentally less toxic  compounds.  A long term goal is to couple DHP to electrodes in order to realize electrocatalytic reactions.  To achieve this goal it will be necessary  to understand its catalytic mechanism and its electron transfer (ET) properties.  In the present study, the fundamental ET properties of DHP  were investigated using protein monolayer electrochemistry (PME), a strategy that involves adsorption of a (sub)monolayer of functional DHP on  a biocompatible electrode.  DHP, which contains a cationic binding site, was electrostatically adsorbed onto anionic carboxylic/hydroxy alkanethiol self-assembled monolayer (SAM) gold electrodes.  To  measure ET rates for the Fe (III) / Fe (II)-oxy redox reaction we used cyclic voltammetry (CV), an electrochemical technique in which current is  measured as a function of scanned potential (voltage). The initial research objective was to obtain a well behaved electrochemical response for  adsorbed DHP that exhibited stability and adequate surface coverage.  This objective was achieved through an optimization study involving the following parameters:  protein purity and storage conditions, SAM composition and assembly time, and solution conditions (buffer type, pH and ionic strength).  The formal potential obtained for adsorbed DHP was  +0.30 V vs. NHE (phosphate buffer; pH 6.00; ionic strength = 6 mM; room temperature).  Measurement of ET rate constants is currently underway to complete this initial study.

 


 

 

Student Author(s): 

Smith, Mychal D.

Home Institution:

Fayetteville State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Molecular and Structural Biochemistry

Research Mentor(s)

Carla Mattos/Molecular and Structural Biochemistry

Paul Swartz/Molecular and Structural Biochemistry

Title of Presentation:

Mapping the Protein Binding Surface of

Insulin using The Multiple Solvent Crystal Structure Method

 

 

Insulin is a polypeptide hormone that regulates carbohydrate metabolism. It is composed of two peptide chains that are linked together by two disulfide bonds.  The aim of this study is to cross-link insulin crystals in order to perform the Multiple Solvent Crystal Structures (MSCS) method. Through the use of organic solvent soaking this method is able to find binding sites, plasticity within these sites, apolar interactions within the binding pockets, and the role of displaceable water molecules. Crystals of this protein were grown using the vapor diffusion method. Two cross-linking agents, Sulfo-EGS and Gluteraldehyde, were used in conjunction with a 10.4 pH phosphate buffer to perform the cross-link.  X-ray crystallography was also used as a tool for screening crystals as well as to check the results of the cross-linking. In conclusion, it was found that the cross-linking of insulin crystals can be performed and further explored using the MSCS method.

 

 


 

 

Student Author(s): 

Smith, Rondell A.

Home Institution:

North Carolina State University

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Animal Science

Research Mentor(s)

H.C Sunny Liu/Animal Science

Title of Presentation:

Protein to Protein Interaction between PRRS Virus ORF4 and Macrophage Host Cell

 

              

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infect macrophages of the immune system of swine. The virus belongs to the Arterivirdae family and is easily spread through nasal secretions, salvia, among other bodily fluids, and can also be carried airborne for up to 2 miles. This virus is detrimental to swine units because it can cause infertility and respiratory problems leading to death. Since swine housing is usually shared the virus has the possibility to affect a large portion of a group because of its long shedding life. This study was done to explore what possible proteins are interacting on open reading frame 4 (ORF4) of the virus infecting the macrophage host cells. ORF4 is important because it is a structural protein on the outside of the virion by which some interaction between it and the host cell could take place.  By performing a yeast two-hybrid we intend to identify novel protein interactions and confirm suspected interactions. With the yeast two-hybrid it utilizes gene transcriptional factors; binding domains (BD) and activation domains (AD), and when fused to two separate proteins that interact with one another the BD and AD are brought together. This allows for transcription to occur of the reporter gene. Yeast growth is then tested to confirm protein interaction through colony lift to measure the B galastosidase activity on the X-gal media and use the lacZ reporter gene which causes positive matings to turn a phenotypic blue. The Data suggest that some kind of interaction takes place but whether it helps for cell adhesion, replication, synthesis, or transport is what is hoped to be identified.

              

 


 

 

Student Author(s): 

Stephenson, Tesia N.

Home Institution:

University of Maryland Baltimore County

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Biological Sciences

Research Mentor(s)

Christian Melander/Chemistry

Title of Presentation:

Synthetic Studies Toward a Representative Model Compound of Lomaiviticin A

 

Lomaiviticin A is a potent antitumor natural product isolated from the marine organism Micromonospora lomaivitiensis. Lomaiviticin A is a novel, homodimeric diazobenzo[b]fluorene glycoside structure that draws similarities to the kinamycin antibiotic family of monomeric diazobenzo[b]fluorenes. Lomaiviticin A induces DNA damage under reducing conditions, and is also effective against gram positive bacteria including Staphylococcus aureus.  Our goal is to build a model compound monomer to which various glycals can be attached that will represent the central core of lomaiviticin A.  These model compounds could then be tested for biological activity, and also studied from a mechanistic point of view to decipher the role the sugars play in interacting with cellular DNA.  The key steps in the synthesis are a nickel catalyzed cross-coupling between a vinyl bromide and grignard reagent.  Osmium tetraoxide mediated dihydroxylation follows to obtain the advanced intermediate.  Methodology work will then need to be done to develop the best conditions for linking the 2’ deoxy sugars of lomaiviticin A to our monomer scaffold.

 


 

 

Student Author(s): 

Sepúlveda, Jennifer

Home Institution:

University of Puerto Rico- Cayey

Program:

NSF Alliances for Graduate Education and the Professoriate (AGEP)

Department(s):

Chemistry

Research Mentor(s)

T. Eric Ballard/Chemistry

Christian Melander/Chemistry

Title of Presentation:

Synthesis of a TAK-779 Gold Nanoparticle Conjugate:  A Highly Potent and Selective Inhibitor of HIV-1 Replication

 

 

CCR5 is known as the major β-chemokine co-receptor for the fusion and entry of HIV-1 into host cells. TAK-779 was identified as a small-molecule nonpeptide CCR5-specific antagonist. Several chemokine antagonists, including TAK-779, have been recently synthesized in an attempt to develop anti-HIV-1 agents. However, HIV-1 mutates to bind around the CCR5-drug complex due to the molecule’s small size. Consequently, over a period of time, the drug is no longer effective. Therefore, to overcome this problem we will synthesize a TAK-779 gold nanoparticle conjugate to suppress the HIV-1 replication. We postulate that conjugation of TAK-779 to the gold nanoparticle will improve drug efficacy by two avenues. First, the size of the nanoparticle is on the order of a small protein; therefore, it will be difficult for HIV-1 to mutate and infect target cells. Second, the increased local concentration of TAK-779 on the nanoparticle will vastly improve the apparent affinity. The eight-step synthesis of our key carboxylic acid intermediate began with reduction of commercially available 4-(4-methylphenyl)benzonitrile to 4-(4-methylphenyl)benzaldehyde  in an 89% yield by the use of Red-Al at -10˚C in THF. Then, a Wittig reaction of this aldehyde with (3-carboxypropyl)triphenylphosphonium bromide and 28% NaOMe in MeOH and followed by hydrogenation at 25 psi overnight led to 5-[4-(4-methylphenyl)phenyl]-4-pentanoic acid in 79% over two steps. Intramolecular acylation of this resulting acid using PPA at 100˚C produced 3-(4-methylphenyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-one in a 51% isolated yield. This compound was treated with sodium methoxide and dimethyl carbonate to produce the corresponding β-ketoester. The resulting ketone was reduced with NaBH4 at -10˚C in THF/water. Treatment with MsCl/Et3N/DBU and concomitant hydrolysis with NaOH provided 59% yield of the 2-(4-Methylphenyl)-6! ,7-dihydro-5H-benzocyclohepten-8-carboxylic acid as the target key intermediate. Further methodological studies will be addressed to achieve the final TAK-779 gold nanoparticle conjugate, which will be tested for its potential CCR5 antagonistic activity in cell culture.

 


 

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