UNEQUIVOCAL SYNTHESIS AND CHARACTERIZATION OF A PARALLEL AND AN ANTIPARALLEL BIS-CYSTINE PEPTIDE

Using an unambiguous methodology we have synthesized the two topologic al isomers (parallel and antiparallel) of a cyclic peptide dimer conta ining two disulfide bridges, and we have characterized them spectrosco pically using circular dichroism and NMR. We have shown that the inter actions between the two chains play a dominant role in determining the different conformational properties of both dimers. Although both mol ecules are flexible, the ensemble of conformations available to them i s clearly different: the antiparallel dimer gives extended structures while the parallel dimer gives mainly folded conformations. Interchain NOEs between symmetry-related residues could be differentiated from t he trivial intraresidue NOE using a selective TOCSY-NOESY experiment, and this assignment was in agreement with the predictions made from a conformational search using molecular dynamics without experimental co nstraints.