A proposed bioactive conformation of peptide T

The conformational profiles of Peptide T, (5-8)Peptide T, [Abu5](4-8)Peptide T and (4-8)Peptide T were computed independently to assess the geometrical characteristics of the bioactive conformation of Peptide T. The conformational profiles of the peptides were computed within the molecular mechanics framework using an effective dielectric constant of 80. The conformational space was thoroughly sampled using an iterative simulated annealing protocol. The bioactive conformation was assessed by pairwise cross comparisons of each of the unique low energy conformations found for each of the different analogs studied. After a putative bioactive conformation was selected, in order to further validate our hypothesis the conformational profile of the potent compound cyclo(Thr-Thr-Asn-Tyr-Thr-Asp) was computed and the putative bioactive conformation was found. The conformation exhibits a pseudo beta-turn involving the side chain of Thr5 and the carbonyl oxygen of Tyr7 forming a C12 ring.