SUBSTITUTION OF AN AMINO-ACID RESIDUE BY LYS FOR CONFORMATIONAL CONSTRAINT OF XAA-ASP FRAGMENT IN BIOLOGICALLY-ACTIVE PEPTIDES BY SIDE-CHAIN LACTAMIZATION

The model cyclopeptide Ac-Lys-Asp-NHMe was used to test Lys as a possi ble substitute for Xaa in peptide fragment Xaa-Asp whose conformationa l mobility would be constrained by lactamization of the Lys and Asp si de chains. By means of theoretical conformational analysis, such a lac tam was shown to be capable of fixing several conformations of the pep tide. Among them, 32 conformations corresponded to 8 low-energy region s of the linear peptide Ac-Ala-Asp-NHMe, which was chosen as a model f or the peptide fragment Xaa-Asp. In this case, the conformational poss ibilities of the Xaa residue were constrained to two regions of the ph i,psi-map, (A + G) and C according to Zimmermann-Sheraga notation.