Arizona Health Sciences

Victor Hruby, Ph.D.

Regents' Professor Emeritus, Department of Chemistry

Contact Information

Office: OC 215

Phone: 520-621-6332
Email: hruby@email.arizona.edu

Honors

  • Murray Goodman Scientific Excellence & Mentorship Award, 2011
  • Arizona Technology Innovator of the Year, 2009
  • Arthur C. Cope Scholar Award, ACS, 2009
  • Ralph F. Hirschmann Award, ACS, 2002
  • Pierce (now Merrifield) Award in Peptide Science, APS, 1993
  • Doctor Honorus Causa, Free University of Brussels, 1989
Research Interests: 

The chemistry of human behavior especially peptide hormones and neurotransmitters; drug design, discovery and development; pain, addiction, feeding behavior, sexual behavior, pigmentation disease, cancer, diabetes, immune response; GPCRs; biophysics/biochemistry of health and disease.

Research Activities: 

Peptide Hormones and Neurotransmitter and Their Receptors and Systems In Health and Disease

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 pepetide 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, bioorganic chemistry, analytical chemistry, physical chemistry, and biology to examine the relationships of structure to information transduction.

II. Synthesis and conformation-bioactivity relationships of alpha, beta, and gamma melanotropins in relation to melanoma cancer, pigmentation, feeding behavior, sexual behavior, energy homeostasis, cardiovascular function, renal function pain, immune response and learning.

We 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.

III. Design and synthesis of conformationally constrained neuropeptides

Conformationally restricted, cyclic, rigid enkephalin, deltorphin, somatostatin, Substance P. cholecystokinin, dynorphin analogues, and related conjugates with high receptor specificity and novel bioactivity profiles are being developed. Using a new design principle we 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. This information is used for de novo peptidomimetic design.

IV. Multivalent Ligands For The Treatment of Disease States

Design, synthesis, and biological evaluation of ligands designed to be agonists at μ and/or δ opioid receptors and antagonist at CCK, NK1 or other receptors relevant to prolonged pain, neuropathic pain, tolerance, and drug seeking behavior.

V. Multimeric Ligands With Scaffolds And Reporter For Defection And Treatment of Disease

We are designing multimeric ligands with appropriate scaffold 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 imagine, and cancer therapeutics.