美国亚利桑那大学化学系：Victor J. Hruby教授的研究小组
Organic Chemistry, Biochemistry and Medicinal Chemistry
Victor J. Hruby
Regents Professor of Chemistry
Professor of Biochemistry
Professor, Arizona Research Laboratories
Professor of Neuroscience
Victor J. Hruby
Office: Old Chemistry 215
Phone: (520) 621-6332
Fax: (520) 621-8407
Education and Appointments:
B.S. 1960, University of North Dakota
M.S. 1962, University of North Dakota
Ph.D. 1965, Cornell University
Ralph F. Hirschmann Award, ACS, 2002
Pierce (now Merrifield) Award in Peptide Science, 1993
Doctor Honorus Causa, Free University of Brussels, 1989
Javits Neuroscience Investigator Award, 1987
Guggenheim Fellow, 1984
Fellow, American Association Advancement of Science, 1972
The 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. They are interested in the rational design of antihormones (inhibitors) based on conformation, in hormone and neurotransmitter receptors, 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. They seek to understand the physical-chemical basis for information transfer 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. Some
1. Asymmetric synthesis of topographically controlled amino acids and their derivatives and β-turn mimetics.
2. Synthesis and conformation-bioactivity relationships of alpha-melanotropin (alpha-MSH) in relation to melanoma cancer, pigmentation, feeding behavior, sexual behavior, cardiovascular function, renal function, pain, and learning.
They have developed conformationally restricted alpha-MSH analogues with extraordinary in vitro and in vivo biological properties including superpotency, superagonist activity, superantagonist activity and super prolonged activity. Computer assisted modeling is being used for design of new scaffolds and more potent and selective compounds including agonists and antagonists for several new melanocortin receptors.
3. Design and synthesis of conformationally constrained neuropeptides. Conformationally restricted, cyclic, rigid enkephalin, deltorphin, somatostatin, cholecystokinin and dynorphin analogues with high receptor specificity and novel bioactivity profiles are being developed. Using a new design principle they are examining the design of ligands that can treat disease states (e.g. neuropathic pain) by design of ligands with overlapping pharmacophores that can simultaneously interact at different receptor types and with different pharmacologies. The conformational basis for their selectivity is being investigated as are new analogues that will modulate pain, behavior, learning, memory, satiety and other CNS effects, and for treatment of AIDS. This information is used in de novo peptidomimetic design.
4. Conformationally constrained oxytocin and vasopressin agonists and antagonists: conformation-biological activity relationships and peptide mimetic design. Design, synthesis and conformational analysis of peptide analogues that can be used to study premature birth, satiety and behavior.
5. They are designing multimeric ligands that can act as molecular machines that will recognize the surface of cancer cells, but not of normal cells, for use in medical diagnosis of cancer, molecular imaging, and cancer therapeutics.
2002年美国化学会国家奖获得者 (ACS 2002 National Award Recipients)
Summary by 杨宏伟 on 2003-12-03
Last updated by 杨宏伟 on 2003-12-03