PREDICTION OF THE BEST LINEAR PRECURSOR IN THE SYNTHESIS OF CYCLOTETRAPEPTIDES BY MOLECULAR MECHANIC CALCULATIONS

Small cyclopeptides of four to six residues are of great interest because of their biological properties (drugs, insecticides, etc.). Identification of a good precursor that is able to undergo cyclization is very important because of the lengthy synthesis of the linear precursors. Several factors are involved in the cyclization yield. In order to determine the relative influence of each factor in this reaction, molecular modeling calculations were performed using the GenMol program. The transition-state energy rather than the dimerization reaction is the determining factor in ring closure, as evidenced by calculations performed on 4-Ala-chlamydocin, HC-toxin analogues, cyclotetrapeptides of sarcosine with glycine, and 4-Ala-chlamydocin and Cyl 2 analogues.