Protein folding: The synthesis and conformational studies on cystinyl-cystinyl-cystine [-CSSCCSSCCSSC-] a novel cross linking motif

Abstract

The cysteine capped, ends protected cross linked motifs 6 and 7, arising from pairs of proximally placed cysteines wherein within a 22 atom framework are inscribed 3 disulphide bridges and 2 peptide linkages, have been prepared and their conformations derived by detailed ¹H NMR studies and molecular modeling protocols, where excellent agreement was seen. Both compounds 6 and 7 possess a C₂ symmetric hydrogen bonded pair involving the peptide NH and the CO of the proximate N-protecting group (Boc or Z). The nature of the latter profoundly influences the conformation. Thus, in 6 where the unit is Boc a bend conformation was promoted by hydrophobic interactions; altematively in 7 with a Z-protecting group the conformation was linear. Compounds 6 and 7 have much promise in diverse aspects of protein design.