CRYSTAL-STRUCTURES OF 2 CYCLIC PSEUDOPENTAPEPTIDES CONTAINING PSI[CH2S] AND PSI[CH2SO] BACKBONE SURROGATES

The solid state conformations of cyclo[Gly-Propsi[CH2S]Gly-D-Phe-Pro] and cyclo[Gly-Propsi[CH2-(S)-SO]Gly-D-Phe-Pro] have been characterized by X-ray diffraction analysis. Crystals of the sulfide trihydrate are orthorhombic, P2(1)2(1)2(1), with a = 10.156(3) angstrom, b = 11.704 (3) angstrom, c = 21.913 (4) angstrom, and Z = 4. Crystals of the sulf oxide are monoclinic, P2(1) with a = 10.662 (1) angstrom, b = 8.552(3) angstrom, c = 12.947(2) angstrom, beta = 94.28(2), and Z = 2. Unlike their all-amide parent, which adopts an all-trans backbone conformatio n and a type II beta-turn encompassing Gly-Pro-Gly-D-Phe, both of thes e peptides contain a cis Gly1-pro2 bond and form a novel turn structur e, i.e., a type II' beta-turn consisting of Gly-D-Phe-Pro-Gly. The tur n structure in each of these peptides is stabilized by an intramolecul ar H bond between the carbonyl oxygen of Gly1 and the amide proton of D-Phe4. In the cyclic sulfoxide, the sulfinyl group is not involved in H bonding despite its strong potential as a hydrogen-bond acceptor. T he crystal structure made it possible to establish the absolute config uration of the sulfinyl group in this peptide. The two crystal structu res also helped identify a type II' beta-turn in the DMSO-d6 solution conformers of these peptides.