Substitution of an Amino Acid Residue by Asp for Conformational Constraint of Lys-Xaa Fragment in Biologically Active Peptides by Side Chain Lactamization

P. V. Kostetsky^1,2 and I. V. Artemjev¹

¹Shemyakin--Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117871 Russia; E-mail: pkos@ibch.siobc.ras.ru

²To whom correspondence should be addressed.

Submitted February 3, 1997; revision submitted April 2, 1997.

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The model cyclic peptide Ac-Lys-Asp-NHMe was used to test Asp as a possible substitute for Xaa in a peptide fragment Lys-Xaa whose conformational mobility would be constrained by lactamization of the Lys and Asp side chains. By means of theoretical conformational analysis, such a lactam was shown to be capable of fixing several conformations of a peptide. Among them, 32 conformations correspond to 8 low-energy regions of the linear peptide Ac-Ala-Ala-NHMe; this was chosen as a model for the peptide fragment Lys-Xaa. In this case, the conformational possibilities of the Lys residue were constrained to two regions of the phi,psi-map (A+G) and (C+F) according to Zimmerman--Scheraga notation. Dihedral angles phi and psi of the Asp residue correspond to lowest-energy areas of phi,psi-map for the Ala residue in linear peptides.

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KEY WORDS: cyclic peptide, theoretical conformational analysis, thymopentin.

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