Crystal and molecular structure of didemnin B, an antiviral and cytotoxic depsipeptide.

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Abstract
Didemnin B, a highly active depsipeptide isolated from a Caribbean tunicate, crystallizes from chloroform/benzene in the orthorhombic space group C2221, with cell parameters a= 14.990 .+-. 0.003 .ANG., b = 22.574 .+-. 0.004 .ANG., c = 41.112 .+-. 0.009 .ANG., V= 13911.7 .ANG.3 at 138 K and a calculaed density of 1.143 g/cm3 based on C57H89N7O15 .cntdot. 1.5C6H6 .cntdot. H2O and eight formula units per cell. The overall agreement factor R = 0.052 for 7699 reflections, 2.theta.max 150.degree., Cu K.hivin..alpha. radiation. The structure determination revealed that didemnin B contains an isostatine residue instead of a statine residue. The conformation of the 23-membered depsipeptide ring is stabilized by one transannular hydrogen bond. The ring does not show the antiparallel .beta.-pleated-sheet structure but, instead, has a fold in the shape of a bent figure-eight. The linear peptide moiety, containing N-methylleucine and lactylproline, forms a .beta.(II)-bend and is folded back toward the cyclic backbone, giving the overall molecule a globular character. Comparison with the structure of cyclosporin A shows distinct stereochemical differences between the two molecules. It is suggested that didemnin B and cyclosporin A are unlikely to have a common receptor binding site.