SYNTHESIS AND SOLVENT EFFECTS ON THE CONFORMATION OF HYMENISTATIN-1

The cyclic octapeptide cyclo(-Pro-Pro-Tyr-Val-Pro-Leu-Ile-Ile-) (1), i solated from the Hymeniacidon sponge, was synthesized and examined con formationally using NMR and molecular-dynamics simulations. Most struc tural parameters of synthetic 1 are in accord with those reported for the isolated material. Our study indicates some small but significant differences in the assignment of the H-1- and C-13-NMR resonances from those of the natural material. The conformation was determined in bot h CHCl3 and DMSO using H-1-NMR and molecular-dynamics simulations. Bot h NOE's and coupling constants were used as experimental restraints du ring the simulations which utilized explicitly the same solvent as in the NMR study. The differences in the interaction of the solvent with 1 were examined, providing insight into the observed differences in co nformation. The dominant conformation contains a betaVIa turn about Il e8-Tyr3 including a Pro1-Pro2 cis-peptide bond and a betaI or betaII t urn about Val4-Ile7 in CHCl3 and DMSO, respectively.