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JOURNAL ARTICLE
RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
REVIEW
Conformational and topographical considerations in the design of biologically active peptides.
Biopolymers 1993 July
An outline of the basic considerations that are under development for the rational design of biologically active peptides and peptidomimetics is given. The necessary interplay of biophysical, chemical, and biological considerations is emphasized. The importance of properly designed biological assays to provide chemical information analogous to that from biophysical studies is discussed. The development of asymmetric synthesis in conjunction with conformational considerations for the preparation of specialized amino acids and amino acid mimetics is a critical aspect of the approach. The overall approach is illustrated with three examples from our laboratory: (1) the redesign of somatostatin to a highly potent and selective mu-opioid receptor antagonist using conformational and topographical considerations in design and for obtaining insights into the pharmacophor; (2) the use of topographical considerations for obtaining oxytocin antagonists; and (3) the application of designer amino acids prepared by asymmetric synthesis to obtain insight into the topographical requirements at delta-opioid receptors.
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