Organic Chemistry, Biochemistry and Medicinal Chemistry
Our research group is interested in the design, synthesis, analysis, conformations, dynamics and structure-biological activity relationships of biologically active peptides and peptide mimetics with special interests in hormones and neurotransmitters that affect human behavior. We are interested in the rational design of antihormones (inhibitors) based on conformation, in hormone and neurotransmitter receptors (GPCRs), in brain chemistry, in the design and asymmetric synthesis of conformationally constrained amino acids, peptides and peptide mimetics, and in the use of NMR and other physical methods to examine peptide and peptidomimetic conformations. We seek to understand the physical-chemical basis for information transduction and for these important molecules in biological systems, and utilize synthetic organic chemistry, structural chemistry, bio-organic chemistry, analytical chemistry, physical chemistry, and biology to examine the relationships of structure to information transduction.
V.J. Hruby, Designing Peptide Receptor Agonists and Antagonists, Nature Reviews Drug Discovery, 1, 847-858 (2002).
P.M. Balse-Srinivasan, P. Grieco, M. Cai, D. Trivedi, and V.J. Hruby, Structure-Activity Relationships of Novel Cyclic α-MSH/β-MSH Hybrid Analogues That Lead to Potent and Selective Ligands for the Human MC3R and Human MC5R, J. Med. Chem., 46, 3728-3733 (2003).
V. J. Hruby, Peptide Science: Exploring the Use of Chemical Principles and Interdisciplinary Collaboration for Understanding Life Processes, J. Med. Chem., 46, 4215-4231 (2003).
I.D. Alves, Z. Salamon, E. Varga, H.I. Yamamura, G. Tollin, and V.J. Hruby, Direct Observation of G-Protein Binding to the Human δ-Opioid Receptor Using Plasmon-Waveguide Resonance Spectroscopy, J. Biol. Chem., 278, 48890-48897 (2003).
J. Ying, K.E. Kövér, X. Gu, G. Han, D.B. Trivedi, M.J. Kavarana, and V.J. Hruby, Solution Structures of Cyclic Melanocortin Agonists and Antagonists by NMR, Biopolymers (Peptide Science), 71, 696-716 (2003).
M. Cai, M. Stankova, S. J.K. Pond, A.V. Mayorov, J.W. Perry, H.I. Yamamura, D. Trivedi, and V.J. Hruby Real Time Differentiation of G-Protein Coupled Receptor (GPCR) Agonist and Antagonist by Two Photon Fluorescence Laser Microscopy, J. Am. Chem. Soc., 126, 7160-7161 (2004).
X. Gu, J. Ying, R.S. Agnes, E. Navratilova, P. Davis, G. Stahl, F. Porreca, H.I. Yamamura, and V.J. Hruby, Novel Design of Bicyclic β-Turn Dipeptides on Solid-Phase Supports and Synthesis of [3.3.0]-Bicyclo[2,3]-Leu-Enkephalin Analogues, Org. Letters, 6, 3285-3288 (2004).
I.D. Alves, K.A. Ciano, V. Boguslavsky, E. Varga, Z. Salamon, H.I. Yamamura, V.J. Hruby, and G. Tollin, Selectivity, Cooperativity, and Reciprocity in the Interactions Between the δ-Opioid Receptor, Its Ligands, and G-Proteins, J. Biol. Chem., 279, 44673-44682 (2004).
V. Subramaniam, I.D. Alves, G.F.J. Salgado, P-W. Lau, R.J. Wysocki, Jr., Z. Salamon, G. Tollin, V.J. Hruby, M.F. Brown, and S.S. Saavedra, Rhodopsin Reconstituted Into a Planar-Supported Lipid Bilayer Retains Photoactivity After Cross-Linking Polymerization of Lipid Monomers, J. Am. Chem. Soc., 127, 5320-5321 (2005).
I.D. Alves, Z. Salamon, V.J. Hruby, and G. Tollin, Ligand Modulation of Lateral Segregation of a G-Protein-Coupled Receptor into Lipid Microdomains in Sphingomyelin/Phosphatidylcholine Solid-Supported Bilayers, Biochemistry, 44, 9168-9178 (2005).
H.L. Handl, J. Vagner, H.I. Yamamura, V.J. Hruby, and R.J. Gillies, Development of a Lanthanide-Based Assay for Detection of Receptor-Ligand Interactions at the Delta-Opioid Receptor, Analytical Biochem., 343, 299-307 (2005).
R.S. Agnes, Y.S. Lee, P. Davis, S-W. Ma, H. Badghisi, F. Porreca, J. Lai, and V.J. Hruby, Structure Activity Relationships of Bifunctional Peptides Based on Overlapping Pharmacophores at Opioid and Cholecystokinin Receptors, J. Med. Chem., 49, 2868-2875 (2006).
D.L. Marks, V. Hruby, G. Brookhart, and R.D. Cone, The Regulation of Food Intake by Selective Stimulation of the Type 3 Melanocortin Receptor (MC3R), Peptides, 27, 259-264 (2006).
J.P. Cain, A.V. Mayorov, M. Cai, H. Wang, B. Tan, K. Chandler, Y.S. Lee, R.R. Petrov, D. Trivedi, and V.J. Hruby, Design, Synthesis, and Biological Evaluation of a New Class of Small Molecule Peptide Mimetics Targeting the Melanocortin Receptors, Bioorg. Med. Chem. Letts., 16, 5462-5467 (2006).
J. Ying, X. Gu, M. Cai, M. Dedek, J. Vagner, D. Trivedi, and V.J. Hruby, Design, Synthesis, and Biological Evaluation of New Cyclic Melanotropin Peptide Analogues Highly Selective for the Human Melanocortin-4 Receptor, J. Med. Chem., 49, 6888-6896 (2006).
T. Yamamoto, P. Nair, P. Davis, S-W. Ma, E. Navratilova, S. Moye, S. Tumati, J. Lai, T.W. Vanderah, H.I. Yamamura, F. Porreca, and V.J. Hruby, Design, Synthesis and Biological Evaluation of Novel Bifunctional C-Terminal Modified for delta/mu Opioid Receptor Agonists and Neurokinin 1 Receptor Antagonists, J. Med. Chem., in press (2007).