Designing peptide receptor agonists and antagonists.
The most ubiquitous mode for controlling and modulating cellular function, intercellular communication, immune response and information-transduction pathways is through peptide-protein non-covalent interactions. Hormones, neurotransmitters, antigens, cytokines and growth factors represent key classes of such peptide ligands. These ligands might either be processed fragments of larger precursor proteins or surface segments of larger proteins. Although there are numerous exceptions, such as insulin, oxytocin and calcitonin, most ligands are not used directly as drugs, and often the most useful ligands for therapy would be analogues that act as antagonists of the native ligands. A search for systematic structure-based or ligand-based approaches to designing such ligands has been an important concern. Today, a robust strategy has been developed for the design of peptides as drugs, drug candidates and biological tools. This strategy includes structural, conformational, dynamic and topographical considerations.
Hruby
Victor J
VJ
Department of Chemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, USA. hruby@email.arizona.edu
D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D010452:Peptide Biosynthesis; D018000:Receptors, Peptide / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
D008024:Ligands; D018000:Receptors, Peptide