Conformational Analysis of the Biologically Active RGD-Containing Anti-adhesive Peptide Cyclo(ArgGlyAspPhe-D-Val)

P. V. Kostetsky^* and I. V. Artemjev

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117871 Russia; E-mail: pkos@ibch.siobc.ras.ru

^* To whom correspondence should be addressed.

Received December 20, 1999; Revision received June 8, 2000

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Using theoretical conformational analysis, the RGD-peptide with anti-adhesive activity cyclo(ArgGlyAspPhe-D-Val) was studied. Random sampling was used to search the conformational space of the allowed torsional angles of the main chain of the molecule. Among 900 stable conformers with different folding of the cyclic moiety of the peptide, only those were selected which corresponded to low-energy conformers of the model linear tripeptide AcAlaGlyAspNHMe. This peptide served as the main chain template of the RGD-fragment of the studied cyclopeptide molecule. Of 36 selected cyclopeptide conformers with potential biological activity, only a few contain stable intramolecular hydrogen bonds. It was supposed that a biologically active conformer of the cyclopeptide molecule exists in solution among other conformers, but not necessarily as the major component of the equilibrium mixture.

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KEY WORDS: cyclopeptide, theoretical conformational analysis, RGD-peptide

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