Design of Peptide Ligands that Interact with Specific Membrane Receptors

  • Victor J. Hruby
  • T. Matsunaga
  • F. Al-Obeidi
  • G. Toth
  • C. Gehrig
  • P. S. Hill
Part of the Industry-University Cooperative Chemistry Program Symposia book series (IUCC)


Peptide hormones and neurotransmitters are carriers of biological information that initiate their biological effects by binding to receptors found on the surface of cells. A basic assumption of modern molecular biology is that the information content of a peptide hormone or neurotransmitter is related to the stereostructural and conformational properties of the peptide. However, the properties of most small (<20 residues) polypeptide hormones and neurotransmitters makes the rational design of such ligands difficult. These properties include: 1) a high degree of conformational flexibility with many conformations accessible at physiological temperatures; 2) a lack of high receptor selectivity; 3) ready biodegration; and 4) the complexity of peptide structures compared with most natural products that have been developed as potential drugs. Despite these difficulties, we and others have developed approaches that show great potential for the systematic rational design of peptide ligands. In this paper we outline some of the approaches that can lead to peptide ligands with high potency, high receptor selectivity, agonist or antagonist activity, high stability against enzymatic breakdown, and conformationally constrained structural properties that provide templates for topographical design and receptor mapping.


Peptide Hormone Peptide Ligand Conformational Flexibility Oxytocin Receptor Side Chain Group 
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Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Victor J. Hruby
    • 1
  • T. Matsunaga
    • 1
  • F. Al-Obeidi
    • 1
  • G. Toth
    • 1
  • C. Gehrig
    • 1
  • P. S. Hill
    • 1
  1. 1.Department of ChemistryUniversity of ArizonaTucsonUSA

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