Relationship between the cyclization and conformation of pentapeptide active esters related to gramicidin S having no protecting group on the side chain of the ornithine residue

Article abstract of DOI:10.1246/bcsj.70.899

To investigate the contribution of the D-phe-Pro-Val sequence in the direct formation of gramicidin S (GS) by the dimerization-cyclization of pentapeptide-active esters having no protecting group on the side chain 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 examined. Only H-D-Phe-Pro-Val-Orn-Leu-ONSu gave semi-GS (cyclic monomer) and GS (cyclic dimer) in yields of 15 and 38%, respectively. The active ester 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 Phe-Pro-Val and Phe-Pro-D-Val sequences did not yield any amount of cyclic monomer and cyclic dimer. The change in the configurations of the Phe and Val residues around the Pro residue greatly affected the CD spectra in ethanol and the ¹H NMR spectra in DMSO-d₆ of the pentapeptide ethyl esters corresponding to four H-X-Pro-Y-Orn-Leu-ONSu's. A good correlation among the CD spectra, NMR spectra of the pentapeptide ethyl esters, and the main products in the cyclization of the active esters was found.