Solution structure of a cyclic rgd peptide that inhibits platelet aggregation

Seetharama D.S. Jois, Usman Sumo Friend, Soma Chakrabarti, Teruna J. Siahaan

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21 Citations (Scopus)

Abstract

Peptides containing the Arg-Gly-Asp (RGD) sequence can inhibit platelet aggregation. Incorporation of this sequence into a cyclic peptide results in specific binding to a particular integrin. Studies of cyclic RGD peptides show that residues surrounding the RGD sequence have important effects on the selectivity of the peptide to bind with glycoprotein Ilb/IIIa (GPIIb/lIIa). In this paper, we elucidate the conformation of cyclo(2,10)Ac-Glyl-Pen2- Gly3-His4-Arg5-Gly6-Asp7-Leu8-Arg9-Cys 10-Ala 11 -NH2 (1) by NMR and molecular dynamics simulations. This peptide inhibits platelet aggregation in a manner similar to that reported for cyclo(2,10)Glyl-Pen2-Gly3-His4-Arg5-Gly6-Asp7-Leu8-Arg9-Cysl0-Alal 1- OH (6) (Cheng, S. et al. J. Med. Chem.1994, 37, 1–8), which is shown to be selective for the GPIIb/IIIa receptor. The cyclic peptide 1 exhibited a major and a minor conformer in solution. In the major conformer, the His4-Arg5-Gly6-Asp7 segment encompasses a 4—>1 hydrogen bond with a distorted type II β-turn, and the minor conformer has turn-extended- turn. A comparison between the major conformation of this peptide and those of other cyclic RGD peptides suggests the importance of a hydrophobic residue adjacent to the RGD sequence.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalJournal of Biomolecular Structure and Dynamics
Volume14
Issue number1
DOIs
Publication statusPublished - 1 Jan 1996

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