SUBSTITUTION BY GLU FOR RESTRICTING THE CONFORMATIONAL FREEDOM OF LYS-XAA FRAGMENTS IN BIOACTIVE PEPTIDES BY SIDE-CHAIN LACTAMIZATION

Using the cyclic peptide Ac-Lys-Glu-NHMe as an example, the possibilit y of using lactamization of the neighboring Lys and Glu residues to re strict the conformational mobility has been examined. As shown by the calculation methods, the lactam can assume quite many conformations, o f which 33 correspond to nine low-energy regions of the linear dipepti de Ac-Ala-Ala-NHMe. In the latter case, the structural variability of the Lys residue is limited to two regions (A+G and C+F in the Zimmerma n-Scheraga nomenclature) on the phi,psi map. The dihedral angles phi a nd psi of the Glu residue may be found in the majority of the conforma tional map regions corresponding to the low-energy regions of an Ala r esidue.