RELATIONSHIP BETWEEN THE CYCLIZATION AND CONFORMATION OF PENTAPEPTIDEACTIVE ESTERS RELATED TO GRAMICIDIN-S HAVING NO PROTECTING GROUP ON THE SIDE-CHAIN OF THE ORNITHINE RESIDUE

To investigate the contribution of the D-Phe-Pro-Val sequence in the d irect formation of gramicidin S (GS) by the dimerization-cyclization o f pentapeptide-active esters having no protecting group on the side ch ain of the Orn residue, the cyclization of four H-X-Pro-Y-Orn-Leu-ONSu 's (X = L- or D-Phe, Y = L- or D-Val, -ONSu = succinimide ester) was e xamined. Only H-D-Phe-Pro-Val-Orn-Leu-ONSu gave semi-GS (cyclic monome r) and GS (cyclic dimer) in yields of 15 and 38%, respectively. The ac tive eater with a D-Phe-Pro-D-Val sequence produced exclusively [D-Val ]-semi-GS in 58% yield. On the other hand, the active esters having Ph e-Pro-Val and Phe-Pro-D-Val sequences did not yield any amount of cycl ic monomer and cyclic dimer. The change in the configurations of the P he and Val residues around the Pro residue greatly affected the CD spe ctra in ethanol and the (HNMR)-H-1 spectra in DMSO-d(6) of the pentape ptide ethyl eaters corresponding to four H-X-Pro-Y-Orn-Leu-ONSu's. A g ood correlation among the CD spectra, NMR spectra of the pentapeptide ethyl eaters, and the main products in the cyclization of the active e aters was found.