SOLUTION CONFORMATION OF CYCLO-(GLY-PRO-SER-D-ALA-PRO) - HYDROGEN-BONDED REVERSE TURNS IN CYCLIC PENTAPEPTIDES

The synthesis and conformational analysis in solution of cyclo-(glycyl-L-prolyl-L-seryl-D-alanyl-L-prolyl) [cyclo-(Gly-Pro-Ser-D-Ala-Pro)] are reported. 1H and 13C NMR results indicate that one conformer (all-trans) predominates in CD2CI2 and Me2SO-d6, and that intramolecular hydrogen bonding involving the Gly N-H is a feature of the preferred conformer. 1H and 13C NMR results suggest a likelihood of a 1←3 hydrogen bond, though not analogous to that observed in the related molecule cyrlo-(Gly-Pro-Gly-D-Ala-Pro). A structure is proposed which contains a D-Ala-Pro type ll' β turn, with the Gly N-H involved in the 1←4 hydrogen bond. The Ser N-H is suggested to participate in the 1←3 interaction though to remain accessible to solvent or other peptide molecules. Comparisons are discussed between the conformer proposed and the crystal structure reported in an accompanying paper. In addition, these structures are compared with other proline-containing cyclic pentapeptides which have been studied. © 1979, American Chemical Society. All rights reserved.