During the past 45+ years, Dr. Hruby and his group have been developing a multidisciplinary approach to the study of peptide hormones and neurotransmitters and their receptors (mostly GPCRs), which has as its major goal developing an understanding of the chemical/physical basis for their effects on human health and disease. This research has involved close collaboration with biologists and medical doctors. They seek to develop peptide and peptidomimetic agonist, antagonist, and inverse agonist ligands that are conformationally constrained and stable in biological environments, can cross (or not) membrane barriers including the blood brain barrier and have unique biological profiles in vivo. They have been highly successful and developed state-of-the-art peptide and peptidomimetic synthesis; asymmetric synthesis of novel chi constrained amino acids, β-turn mimetics, etc. and their chimeric derivatives; computational chemistry and molecular modeling including binding to GPCRs of interest; development of state-of-the-art NMR methods to study peptide and peptidomimetic conformations in solution and in membrane environments, and conformations when interacting (binding) to their receptors.
They have developed selective and biologically stable agonists and antagonists for use in biological systems including oxytocin agonist and antagonist ligands that are potent and selective for peripheral and brain receptors, melanotropin agonist and antagonist analogues for the melanocortin 1, 3, 4 and 5 receptors, and novel cyclic and constrained ligands that are potent and selective analogues for the mu, delta or kappa opioid receptors, ligands that are potent and selective for bradykinin receptors, and cholecystokinin receptors, and multivalent ligands of various compositions and structural types. With biological and medical colleagues we have demonstrated in vivo biological activities in health and disease related to maternal behavior, learning behavior, sexual behavior, including psychogenic erectile dysfunction, feeding behavior including obesity and anorexia, immune response, pigmentary response including melanoma cancer and cancer prevention, pain including prolonged and neuropathic pain, etc. With our medical colleagues we have done several clinical trials, and are prepared to do more when given the opportunity.
- Sawyer, T.K.,Sanfilippo, P.J., Hruby, V.J., Engel, M.H., Heward, C.B., Burnett, J.B., and Hadley, M.E., [Nle4, D-Phe7]-α-Melanocyte Stimulating Hormone: A Highly Potent α-Melanotropin with Ultralong Biological Activity, Proc. Natl. Acad. Sci. U.S.A., 77, 5754-5758 (1980).
- Al-Obeidi, F., Hadley, M.E., Pettitt, B.M.and Hruby, V.J., Design of a New Class of Superpotent Cyclic α-Melanotropins Based on Quenched Dynamic Simulations, J. Amer. Chem. Soc., 111, 3413-3416 (1989).
- Fan W., Boston, B.A., Kesterson, R.A., Hruby, V.J. and Cone, R.D., Role of Melanocortinergic Neurons in Feeding and the Agouti Obesity Syndrome, Nature, 385, 165-168 (1997).
- Hruby, V.J., Designing Peptide Receptor Agonists and Antagonists, Nature Reviews Drug Discovery, 1, 847-858 (2002).
- Mosberg, H.I., Hurst, R., Hruby, V.J., Gee, K., Yamamura, H.I., Galligan, J.J. and Burks, T.F., Bis-Penicillamine Enkephalins Possess Highly Improved Specificity Toward Delta Opioid Receptors, Proc. Natl. Acad. Sci. U.S.A., 80, 5871-5874 (1983).
- Hruby, V.J. Hruby, Kao, L-F., Pettitt, B.M. and Karplus, M., The Conformational Properties of the Delta Opioid Peptide [D-Pen2, D-Pen5]-enkephalin in Aqueous Solution Determined by NMR and Energy Minimization Calculations, J. Am. Chem. Soc., 110, 3351-3359 (1988).
- Cai, M., Nyberg, J. and Hruby, V.J., Melanotropins as Drugs for the Treatment of Obesity and Other Feeding Disorders: Potential and Problems, Curr. Topics Med. Chem., 9, 554-563 (2009).
- Flippen-Anderson, J.L., Hruby, V.J., Collins,N., George, C. and Cudney, B., X-Ray Structure of [D-Pen2, D-Pen5]Enkephalin, A Highly Potent, Delta Opioid Receptor Selective Compound: Comparisons With Proposed Solution Conformations, J.Am. Chem. Soc., 116, 7523-7531 (1994).
- Nicolás, E. Russell, K.C. and Hruby, V.J., Asymmetric 1,4-Addition of Organocuprates to Chiral α,β-Unsaturated N-Acyl-4-Phenyl-2-Oxazolidinones: A New Approach to the Synthesis of Chiral β-Branched Carboxylic Acids, J. Org. Chem., 58, 766-770 (1993).
- Qian, X., Russell, K.C., Boteju, L.W. and Hruby, V.J., Stereoselective Total Synthesis of Topographically Constrained Designer Amino Acids: 2', 6'-Dimethyl-β-Methyltyrosines, Tetrahedron, 51, 1033-1054 (1995).
- Soloshonok, V.A., Cai, C., Yamada, T., Ueki, H., Ohfune, Y. and Hruby, V.J., Michael Addition Reactions between Chiral Equivalents of a Nucleophilic Glycine and (S)- or (R)-3-[(E)-Enoyl]-4-phenyl-1,3-oxazolidin-2-ones as a General Method for Efficient Preparation of β-Substituted Pyroglutamic Acids. Case of Topographically Controlled Stereoselectivity, J. Am. Chem. Soc., 127, 15296-15303 (2005). PMC1851941
- Liu, Z., Mehta, S.J. and Hruby, V.J., Strategies for Asymmetric Synthesis of Amino Acids with δ/γ- Unsaturation’, Organic Preparations and Procedures International, 44, 222-255 (2012).
- Lam, K.S., Salmon, S.E., Hersh, E.M., Hruby, V.J., Kazmierski, W.M. and Knapp, R.J., A New Type of Synthetic Peptide Library for Identifying Ligand-Binding Activity, Nature, 354, 82-84 (1991).
- Lam, K.S., Hruby, V.J., Lebl, M., Knapp, R.J., Kazmierski, W.M., Hersh, E.M. and Salmon, S.E., The Chemical Synthesis of Large Random Peptide Libraries and Their Use For the Discovery of Ligands for Macromolecular Acceptors, Bioorganic & Medicinal Chemistry Letters, 3, 419-424 (1993).
- Hruby, V.J., Synthesis of Peptide Libraries for Lead Structure Screening, The Practice of Medicinal Chemistry, C.G. Wermuth, Ed., Academic Press, London, Chapter 9, 135-151 (1996).
- Horan, P.J., Mattia, A., Bilsky, E.J., Weber, S.J., Davis, T.P., Yamamura, H.I., Malatynska, E., Applyard, S.M., Slaninová, J., Misicka, A., Lipkowski, A.W., Hruby, V.J. and Porreca, F., Antinociceptive Profile of Biphalin, A Dimeric Enkephalin Analog, J. Pharmacol. Exp. Ther., 265, 1446-1454 (1993).
- Hruby, V.J., Porreca, F., Yamamura, H.I., Tollin, G., Agnes, R.S., Lee, Y.S., Cai, M., Alves, I., Cowell, S., Varga, E., Davis, P., Salamon, Z., Roeske, W., Vanderah, T. and Lai, J., New Paradigms and Tools in Drug Design for Pain and Addiction, Am. Assoc. Pharm. Sci. J., 8(3), E450-E460 (2006). PMCID: PMC1764851
- Yamamoto, T., Nair, P., Jacobsen, N.E., Davis, P., Ma, S-W, Navratilova, E., Moye, S., Lai, J., Yamamura, H.I., Vanderah, T.W., Porreca, F. and Hruby, V.J., The Importance of Micelle-Bound States for the Bioactivities of Bifunctional Peptide Derivatives for δ/μ Opioid Receptor Agonists and Neurokinin 1 Receptor Antagonists, J. Med. Chem., 51, 6334-6347 (2008). PMC18821747
2005-Present Professor of Medical Pharmacology, University of Arizona
2005-Present Professor of BIO5, University of Arizona
1989-Present Regents Professor, University of Arizona
1982-Present Professor of Arizona Research Laboratory (Joint Appointment), University of Arizona
1978-Present Professor of Biochemistry and Molecular Biophysics (Joint Appointment), University of Arizona
1977-Present Professor of Chemistry, University of Arizona
1975-1976 Guest Worker (NIH Research Fellowship), NIH (with Martin Rodbell)
1972-1977 Associate Professor, University of Arizona
1968-1972 Assistant Professor, University of Arizona
1967-1968 Research Associate, Cornell University (with Vincent du Vigneaud)
1965-1967 Instructor of Biochemistry, Cornell University Medical College
2012 Roche-Meienhofer Award
2012 ACS Medicinal Chemistry Hall of Fame
2011 Murray Goodman Award (APS)
2009 Arthur C. Cope Scholar Award (ACS)
2009 Arizona Technology Innovator of the Year
2007 Goodman Lecturer, UCSD
2006 Distinguished Career Teaching Award, University of Arizona
2003 Nolan and Gloria Sommer Award
2002 Ralph T. Hirschmann Award (ACS)
2002 Cathay Award (China)
1999-2000 Humboldt Senior Scientist Award
1996 Blomquist Lecturer, Cornell
1993 Pierce (ne Merrifield) Award (APS)
1989 Doctor Honorus Causa, Free University of Brussels
1988 MERIT Award
1987 Javits Neuroscience Award
1984-1985 Guggenheim Fellowship
1981 Fellow - N.Y. Acad. Sci.
1979 Fulbright-Hays Fellow
1978-1979 Rector's Lectureship, Free Univ. of Brussels
1975-1976 Fellow - Am. Ins. of Chemists; PHS Fellow; Fellow - AAAS
1963-1965 Cornell University - NSF Cooperative Fellow
1960 University of North Dakota - Abbott Award; Coon Award; Magna cum laude
2007-2012 Member, Drug Discovery Panel ZRG1 MNPS-C (09) F Study Section, NIH
2002 Co-Chair, Gordon Research Conference
2000-2005 Member, Special Emphasis Panel MDCN-5 Study Section, NIH
1999-2000 Visiting Professor, Technical Univ. Munich (with Horst Kessler), Senior Humboldt Fellow
1997-2006 Editor-in-Chief, J. Peptide Research
1993 Visiting Professor, California Institute of Technology (with Peter Dervan),
1993 Organized Keystone Symposium
1990-1991 President, American Peptide Society
1988-1996 Editor-in-Chief, Int. J. Peptide Protein Research
1987-1992 Editorial Board, J. Med. Chem. and currently 8 others
1985-1989 Member, Bio-organic and Natural Product Chemistry Study Section, NIH
1984-1991 Editorial Board, Life Sciences
1984-1985 Visiting Professor, Harvard University, (with Martin Karplus)
1983 Chairman, American Peptide Symposium, 1981-1983; Organized 8th Am. Peptide Symp.
1981-2006 Editorial Board, Journal of Protein Chemistry
1980-1984 Member, Physiological Chemistry Study Section, NIH
1979-1990 American Peptide Symposium Board, Secretary/Treasurer
1979 Rector's Lecturer, Free University of Brussels