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Concept and progress in the development of RGD‐containing peptide pharmaceuticals
Author(s) -
Craig William S.,
Cheng Soan,
Mullen Daniel G.,
Blevitt Jon,
Pierschbacher Michael D.
Publication year - 1995
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360370209
Subject(s) - chemistry , peptide , combinatorial chemistry , nanotechnology , biochemistry , materials science
The cell adhesion domain, arginine–glycine–aspartic acid (RGD), has been incorporated into synthetic peptides to perform either of two modes of drug action, antagonist or agonist. Short, conformationally constrained peptides have been developed as antagonists for the platelet membrane glycopivtein complex, the integrin α IIb β 3 , using cell‐based and integrin‐based assays. In combination with a comparative molecular modeling study, these results have helped identify common conformalional elements in the pharmacophore of this class of molecules. Peptides are presented that are highly potent, integrin specific, and that possess reduced pharmacological side effects. Also presented is the development of a peptide that modifies, noncovalently, the surfaces of a wide variety of this molecule is evident from its ability to stimulate cell attachment on these surfaces. This is shown to translate into an in vivo activity of faster and more complete tissue integration, and a reduction in foreign body response. © 1994 John Wiley & Sons, Inc.