Chemicals and Drugs Commons^™

Distribution Of Allatostatin C-Like Immunoreactivity In The Central Nervous System Of The Copepod Crustacean Calanus Finmarchicus, Caroline H. Wilson, Andrew E. Christie

Health Sciences and Kinesiology Faculty Articles

The C-type allatostatins (C-ASTs) are a family of highly pleiotropic arthropod neuropeptides. In crustaceans, transcriptomic/mass spectral studies have identified C-ASTs in the nervous systems of many species; the cellular distributions of these peptides remain unknown. Here, the distribution of C-AST was mapped in the nervous system of the copepod Calanus finmarchicus, the major contributor to the North Atlantic’s zooplanktonic biomass; C-AST-immunopositive neurons were identified in the protocerebrum, in several peripheral ganglia associated with feeding appendages, and in the ganglia controlling the swimming legs, with immunopositive axons present throughout the ventral nerve cord. In addition, axons innervating the dorsal longitudinal …

5¢-O-B,G-Methylenetriphosphate Derivatives Of Nucleoside, Yousef Ahmadibeni, Chandravanu Dash, S. F. J. Le Grice, Keykavous Parang

Pharmacy Faculty Articles and Research

The solid-phase synthesis of 5¢-O-b,g-methylenetriphosphates of nucleosides 1–5 is described, where a 4-acetoxy-3-arylbenzyloxy group was used as a linker.

Impaired M3 And Enhanced M2 Muscarinic Receptor Contractile Function In A Streptozotocin Model Of Mouse Diabetic Urinary Bladder, K. J. Pak, Rennolds S. Ostrom, M. Matsui, F. J. Ehlert

Pharmacy Faculty Articles and Research

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after …

Plasma Pharmacokinetics And Tissue Disposition Of Novel Dextran- Methylprednisolone Conjugates With Peptide Linkers In Rats, Suman Penugonda, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Pharmacy Faculty Articles and Research

The plasma and tissue disposition of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP-1) or five (DMP-5) amino acids as linkers were studied in rats. Single 5-mg/kg doses (MP equivalent) of each prodrug or MP were administered intravenously, and blood and tissue samples were collected. Prodrug and drug concentrations were quantitated using HPLC, and noncompartmental pharmacokinetic parameters were estimated. Whereas conjugation of MP with dextran in both prodrugs substantially decreased the clearance of the drug by ∼200-fold, the accumulations of the drug in the liver, spleen, and kidneys were significantly increased by conjugation. However, the extent of accumulation …

Hcmv Pus28 Initiates Pro-Migratory Signaling Via Activation Of Pyk2 Kinase, Jennifer Totonchy, Susan Varnum, Ryan Melnychuk, Patricia Smith, Ljiliana Pasa-Tolic, Janani I. Shutthanadan, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Background: Human Cytomegalovirus (HCMV) has been implicated in the acceleration of vascular disease and chronic allograft rejection. Recently, the virus has been associated with glioblastoma and other tumors. We have previously shown that the HCMV-encoded chemokine receptor pUS28 mediates smooth muscle cell (SMC) and macrophage motility and this activity has been implicated in the acceleration of vascular disease. pUS28 induced SMC migration involves the activation of the protein tyrosine kinases (PTKs) Src and Focal adhesion kinase as well as the small GTPase RhoA. The PTK Pyk2 has been shown to play a role in cellular migration and formation of cancer, …

Synthesis And Evaluation Of Conformationally Constrained Peptide Analogues As The Src Sh3 Domain Binding Ligands, Rakesh Tiwari, Alex Brown, Seetha Narramaneni, Gongqin Sun, Keykavous Parang

Pharmacy Faculty Articles and Research

Src kinase activity is regulated by the interaction of SH3 domain with protein sequences that are rich in proline residues. Identification of more potent SH3 domain binding ligands that can regulate Src kinase activity is a subject of major interest. Conformationally constrained peptides have been previously used for improving the binding potency of the Src SH2 domain binding peptide ligands and peptide substrates of the substrate-binding site of Src. A series of peptide analogues of Ac-VSLARRPLPPLP (1, Ac-VSL-12, Kd = 0.34 M) were synthesized by introducing conformational constraints to improve the binding affinity towards the Src SH3 domain. Peptides synthesized …

The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3a Receptor-Mediated Currents In Xenopus Laevis Oocytes, Keun-Hang Susan Yang, Sehamuddin Galadari, Dmytro Isaev, Georg Petroianu, Toni S. Shippenberg, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)3A receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 μM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 μM). CBD (1 μM) did not alter specific binding of the 5-HT3A antagonist [3H]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl)propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 μM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 μM, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 …

Prospects And Pits On The Path Of Biomimetics: The Case Of Tooth Enamel, Vuk Uskoković

Pharmacy Faculty Articles and Research

This review presents a discourse on challenges in understanding and imitating the process of amelogenesis in vitro on the molecular scale. In light of the analysis of imitation of the growth of dental enamel, it also impends on the prospects and potential drawbacks of the biomimetic approach in general. As the formation of enamel proceeds with the protein matrix guiding the crystal growth, while at the same time conducting its own degradation and removal, it is argued that three aspects of amelogenesis need to be induced in parallel: a) crystal growth; b) protein assembly; c) proteolytic degradation. A particular emphasis …

Intravenous Artesunate For Severe Malaria, Karl M. Hess, Jeffery A. Goad, Paul M. Arguin

Pharmacy Faculty Articles and Research

OBJECTIVE: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria.

DATA SOURCES: Literature was retrieved through PubMed (1999 March 2010), MEDLINE (1996 March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles in English that were identified from the data sources were reviewed. Focus was placed on post-marketing trials examining the safety and efficacy of artesunate in comparison with other regimens.

DATA SYNTHESIS …

Synthesis Of Nucleoside 5′-O-Α,Β-Methylene-Β-Triphosphates And Evaluation Of Their Potency Towards Inhibition Of Hiv-1 Reverse Transcriptase, Yousef Ahmadibeni, Chandravanu Dash, M. J. Hanley, S. F. J. Le Grice, Hitesh K. Agarwal, Keykavous Parang

Pharmacy Faculty Articles and Research

A polymer-bound α,β-methylene-β-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5′-O-α,β-methylene-β-triphosphates. Among all the compounds, cytidine 5′-O-α,β-methylene-β-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a Ki value of 225 μM.

Development Of Cytarabine Prodrugs And Delivery Systems For Leukemia Treatment, Bhupender S. Chhikara, Keykavous Parang

Pharmacy Faculty Articles and Research

Importance of the field: Cytarabine is a polar nucleoside drug used for the treatment of myeloid leukemia and non-Hodgkin’s lymphoma. The drug has a short plasma half-life, low stability, and limited bioavailability. Overdosing of patients with continuous infusions may lead to side effects. Thus, various prodrug strategies and delivery systems have been extensively explored to enhance the half-life, stability, and delivery of cytarabine. Among the recent cytarabine prodrugs, amino acid conjugate ValCytarabine and fatty acid derivative CP-4055 (in phase 3 trials) have been investigated for the treatment of leukemia and solid tumors, respectively. Alternatively, delivery systems of cytarabine have …

Synthesis, Antiviral And Contraceptive Activities Of Nucleoside-Sodium Cellulose Sulfate Acetate And Succinate Conjugates, Hitesh K. Agarwal, Anil Kumar, Gustavo F. Doncel, Keykavous Parang

Pharmacy Faculty Articles and Research

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2',3'-dideoxy-3'-thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfate-acetate (CSA) (e.g., AZT-CSA and FLT-CSA) were found to be more potent than CS and other conjugates (e.g., AZT-succinate-CS, and FLT-succinate-CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type …

Trnas: Cellular Barcodes For Amino Acids, Ranat Banerjee, Shawn Chen, Kiley Dare, Marla Gilreath, Mette Praetorius-Ibba, Medha Raina, Noah M. Reynolds, Theresa E. Rogers, Hervé Roy, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The role of tRNA in translating the genetic code has received considerable attention over the last 50 years, and we now know in great detail how particular amino acids are specifically selected and brought to the ribosome in response to the corresponding mRNA codon. Over the same period, it has also become increasingly clear that the ribosome is not the only destination to which tRNAs deliver amino acids, with processes ranging from lipid modification to antibiotic biosynthesis all using aminoacyl‐tRNAs as substrates. Here we review examples of alternative functions for tRNA beyond translation, which together suggest that the role of …

Broad Range Amino Acid Specificity Of Rna-Dependent Lipid Remodelling By Multiple Peptide Resistance Factors, Hervé Roy, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacylphosphatidylglycerol synthases (aaPGSs) are multiple peptide resistance factors that transfer amino acids from aminoacyl-tRNAs to phosphatidylglycerol (PG) in the cytoplasmic membrane. Aminoacylation of PG is used by bacteria to decrease the net negative charge of the cell envelope, diminishing affinity for charged molecules and allowing for adaptation to environmental changes. Lys-PGS, which transfers lysine to PG, is essential for the virulence of certain pathogens, providing resistance to both host cationic antimicrobial peptides and therapeutic antibiotics. Ala-PGS was also recently described, but little is known about the possible activities of other members of the highly diverse aaPGS family of proteins. Systematic …

The Cca Anticodon Specifies Separate Functions Inside And Outside Translation In Bacillus Cereus, Sandro F. Ataide, Theresa E. Rogers, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacillus cereus 14579 encodes two tRNAs with the CCA anticodon, tRNA^Trp and tRNA^Other. tRNA^Trp was separately aminoacylated by two enzymes, TrpRS1 and TrpRS2, which share only 34% similarity and display different catalytic capacities and specificities. TrpRS1 was 18-fold more proficient at aminoacylating tRNA^Trp with Trp, while TrpRS2 more efficiently utilizes the Trp analog 5-hydroxy Trp. tRNA^Other was not aminoacylated by either TrpRS but instead by the combined activity of LysRS1 and LysRS2, which recognized sequence elements absent from tRNA^Trp. Polysomes were found to contain tRNA^Trp, consistent with its role in …

The Proteolytic Stability And Cytotoxicity Studies Of L‐Aspartic Acid And L‐Diaminopropionic Acid Derived Β‐Peptides And A Mixed Α/Β‐Peptide, Sahar Ahmed, Kamaljit Kaur

Pharmacy Faculty Articles and Research

The use of peptides as drugs in pharmaceutical applications is hindered by their susceptibility to proteolysis and therefore low bioavailability. β‐Peptides that contain an additional methylene group in the backbone, are gaining recognition from a pharmaceutical stand point as they are considerably more resilient to proteolysis and metabolism. Recently, we reported two new classes of β‐peptides, β³‐ and β²‐peptides derived from l‐aspartic acid and l‐diaminopropionic acid, respectively. Here, we report the proteolytic stability of these β‐peptidic compounds and a mixed α /β‐peptide against three enzymes (pronase, trypsin and elastase), as well as, human serum. The …

Resampling And Editing Of Mischarged Trna Prior To Translation Elongation, Jiqiang Ling, Byung Ran So, Srujana S. Yadavalli, Hervé Roy, Shinichiro Shoji, Kurt Fredrick, Karin Musier-Forsyth, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Faithful translation of the genetic code depends on the GTPase EF-Tu delivering correctly charged aminoacyl-tRNAs to the ribosome for pairing with cognate codons. The accurate coupling of cognate amino acids and tRNAs by the aminoacyl-tRNA synthetases is achieved through a combination of substrate specificity and product editing. Once released by aminoacyl-tRNA synthetases, both cognate and near-cognate aminoacyl-tRNAs were considered to be committed to ribosomal protein synthesis through their association with EF-Tu. Here we show instead that aminoacyl-tRNAs in ternary complex with EF-Tu•GTP can readily dissociate and rebind to aminoacyl-tRNA synthetases. For mischarged species, this allows resampling by the product editing …

New Dosing Schedules Of Dasatinib For Cml And Adverse Event Management, Siu Fun Wong

Pharmacy Faculty Articles and Research

Resistance to imatinib in patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has emerged as a significant clinical issue. Dasatinib is a tyrosine kinase inhibitor that has 325-fold greater in vitro activity against native BCR-ABL (breakpoint cluster region-Abelson leukemia virus) compared with imatinib and can overcome primary (intrinsic) and secondary (acquired) imatinib resistance. Here, we review the clinical profile of dasatinib in imatinib-resistant and -intolerant patients and share clinical approaches for managing adverse events (AEs) to ensure maximum patient benefit. References were obtained through literature searches on PubMed as well as from the Proceedings …

Adaptation Of The Bacterial Membrane To Changing Environments Using Aminoacylated Phospholipids, Hervé Roy, Kiley Dare, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fine‐tuning of the biophysical properties of biological membranes is essential for adaptation of cells to changing environments. For instance, to lower the negative charge of the lipid bilayer, certain bacteria add lysine to phosphatidylglycerol (PG) converting the net negative charge of PG (−1) to a net positive charge in Lys‐PG (+1). Reducing the net negative charge of the bacterial cell wall is a common strategy used by bacteria to resist cationic antimicrobial peptides (CAMPs) secreted by other microbes or produced by the innate immune system of a host organism. The article by Klein et al. in the current issue of …

Human Cytomegalovirus Us28: A Functionally Selective Chemokine Binding Receptor, Jennifer Totonchy, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is the most well-characterized of the four chemokine receptor-like molecules found in the HCMV genome. US28 been studied as an important virulence factor for HCMV-mediated vascular disease and, more recently, in models of HCMV-associated malignancy. US28 is a rare multi-chemokine family binding receptor with the ability to bind ligands from two distinct chemokine classes. Ligand binding to US28 activates cell-type and ligand-specific signaling pathways leading to cellular migration, an example receptor functional selectivity. Additionally, US28 has been demonstrated to constitutively activate PLC and NFkB. Understanding the structure/function relationships between US28, its ligands and …

Isoniazid Completion Rates For Latent Tuberculosis Infection Among College Students Managed By A Community Pharmacist, Karl M. Hess, Jeffery A. Goad, Joanne Wu, Kathleen Johnson

Pharmacy Faculty Articles and Research

Objective: The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy oil a college Campus. and to describe patient characteristics. Participants: Participants were university Students diagnosed with LTBI. Methods: The authors conducted a retrospective review, of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken. characteristics of completers versus noncompleters. average time to treatment completion, and reported adverse drug events. Results: The 9-month completion rate was 59%, and the …

The First Total Synthesis Of (±)-4-Methoxydecanoic Acid: A Novel Antifungal Fatty Acid, Nestor Carballeira, Carlos Miranda, Keykavous Parang

Pharmacy Faculty Articles and Research

The hitherto unknown (±)-4-methoxydecanoic acid was synthesized in six steps and in 25% overall yield starting from commercially available 4-penten-1-ol. The title compound demonstrated 17-fold higher antifungal activity (MIC = 1.5 mM) against Candida albicans ATCC 60193 and Cryptococcus neoformans ATCC 66031 when compared to unsubstituted n-decanoic acid. Our results demonstrate that mid-chain methoxylation appears to be a viable strategy for increasing the fungitoxicity of fatty acids.

The Guinea Pig Ileum Lacks The Direct, High-Potency, M2-Muscarinic, Contractile Mechanism Of The Mouse Ileum, Michael T. Griffin, Minoru Matsui, Rennolds S. Ostrom, Frederick J. Ehlert

Pharmacy Faculty Articles and Research

We explored whether the M2 muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M3 muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M3 selectivity. Then, we used 4-DAMP mustard to inactivate M3 responses in the guinea pig ileum to attempt to reveal direct, M2 receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M2 receptor knockout, and M3 receptor knockout mice characterized by negative log EC50 (pEC50) values ± SEM of …

Rat Cytomegalovirus Infection Depletes Mhc Ii In Bone Marrow Derived Dendritic Cells, Carmen C. Baca Jones, Craig N. Kreklywich, Ilhem Messaoudi, Jennifer Totonchy, Erin Mccartney, Susan L. Orloff, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

While cytomegalovirus (CMV) infects and replicates in a multitude of cell types, the ability of the virus to replicate in antigen presenting cells (APCs) is believed to play a critical role in the viral dissemination and latency. CMV infection of APCs and manipulation of their function is an important area of investigation. CMV down regulation of MHC II is reportedly mediated by the HCMV proteins US2, US3, UL83, UL111a (vIL10) or through the induction of cellular IL10. In this study, we demonstrate that rat CMV (RCMV) significantly reduces MHC II expression by mechanisms that do not involve orthologues of the …

Differential Ligand Binding To A Human Cytomegalovirus Chemokine Receptor Determines Cell Type-Specific Motility, Jennifer Totonchy, Ryan Melnychuk, Patricia P. Smith, Joshua Powell, Laurel Hall, Victor R. Defilippis, Klaus Fruh, Martine Smit, David D. Schlaepfer, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

While most chemokine receptors fail to cross the chemokine class boundary with respect to the ligands that they bind, the human cytomegalovirus (HCMV)-encoded chemokine receptor US28 binds multiple CC-chemokines and the CX3Cchemokine Fractalkine. US28 binding to CC-chemokines is both necessary and sufficient to induce vascular smooth muscle cell (SMC) migration in response to HCMV infection. However, the function of Fractalkine binding to US28 is unknown. In this report, we demonstrate that Fractalkine binding to US28 not only induces migration of macrophages but also acts to inhibit RANTES-mediated SMC migration. Similarly, RANTES inhibits Fractalkine-mediated US28 migration in macrophages. While US28 binding …

Synthesis And Evaluation Of Phosphopeptides Containing Iminodiacetate Groups As Binding Ligands Of The Src Sh2 Domain, Guofeng Ye, Aaron D. Schuler, Yousef Ahmadibeni, Joel R. Morgan, Absar Faruqui, Kezhen Huang, Gongqin Sun, John A. Zebala, Keykavous Parang

Pharmacy Faculty Articles and Research

Phosphopeptide pTyr-Glu-Glu-Ile (pYEEI) has been introduced as an optimal Src SH2 domain ligand. Peptides, Ac-K(IDA)pYEEIEK(IDA) (1), Ac-KpYEEIEK (2), Ac-K(IDA)pYEEIEK (3), and Ac-KpYEEIEK(IDA) (4), containing 0–2 iminodiacetate (IDA) groups at the N- and C-terminal lysine residues were synthesized and evaluated as the Src SH2 domain binding ligands. Fluorescence polarization assays showed that peptide 1 had a higher binding affinity (Kd = 0.6 μM) to the Src SH2 domain when compared with Ac-pYEEI (Kd = 1.7 μM), an optimal Src SH2 domain ligand, and peptides 2–4 (Kd = 2.9–52.7 μM). The binding affinity of peptide 1 to the SH2 domain was reduced …

The C1 And C2 Domains Target Human Type 6 Adenylyl Cyclase To Lipid Rafts And Caveolae, Muthusamy Thangavel, Xiaoqiu Liu, Shu Qiang Sun, Joseph Kaminsky, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Previous data has shown that adenylyl cyclase type 6 (AC6) is expressed principally in lipid rafts or caveolae of cardiac myocytes and other cell types while certain other isoforms of AC are excluded from these microdomains. The mechanism by which AC6 is localized to lipid rafts or caveolae is unknown. In this study, we show AC6 is localized in lipid rafts of COS-7 cells (expressing caveolin-1) and in HEK-293 cells or cardiac fibroblasts isolated from caveolin-1 knock-out mice (both of which lack prototypical caveolins). To determine the region of AC6 that confers raft localization, we independently expressed each of the …

Incentives For Orphan Drug Research And Development In The United States, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio, Sheryl L. Szeinbach, Jay Visaria

Pharmacy Faculty Articles and Research

Background: The Orphan Drug Act (1983) established several incentives to encourage the development of orphan drugs (ODs) to treat rare diseases and conditions. This study analyzed the characteristics of OD designations, approvals, sponsors, and evaluated the effective patent and market exclusivity life of orphan new molecular entities (NMEs) approved in the US between 1983 and 2007.

Methods: Primary data sources were the FDA Orange Book, the FDA Office of Orphan Drugs Development, and the US Patent and Trademark Office. Data included all orphan designations and approvals listed by the FDA and all NMEs approved by the FDA during …

Helical Peptides Derived From Lactoferrin Bind Hepatitis C Virus Envelope Protein E2, Reem Beleid, Donna Douglas, Norman Kneteman, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Hepatitis C virus is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma infecting more than 170 million people. Hepatitis C virus envelope 2 glycoprotein (E2) binds several cell‐surface molecules that act as receptor candidates mediating hepatitis C virus entry into hepatocytes. Peptides derived from human lactoferrin have been shown to bind hepatitis C virus‐E2 protein thereby preventing hepatitis C virus entry in cultured hepatocytes. In this study, starting from a 33‐residue human lactoferrin‐derived peptide, a number of biotin‐linked α‐peptides were synthesized and investigated for their E2 protein binding activity. E2 protein from hepatitis C virus genotype 1b …

Aminoacyl-Trna Synthetase Complexes: Molecular Multitasking Revealed, Corinne D. Hausmann, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The accurate synthesis of proteins, dictated by the corresponding nucleotide sequence encoded in mRNA, is essential for cell growth and survival. Central to this process are the aminoacyl-tRNA synthetases (aaRSs), which provide amino acid substrates for the growing polypeptide chain in the form of aminoacyl-tRNAs. The aaRSs are essential for coupling the correct amino acid and tRNA molecules, but are also known to associate in higher order complexes with proteins involved in processes beyond translation. Multiprotein complexes containing aaRSs are found in all three domains of life playing roles in splicing, apoptosis, viral assembly, and regulation of transcription and translation. …