PROTEIN-FOLDING - THE SYNTHESIS AND CONFORMATIONAL STUDIES ON CYSTINYL-CYSTINYL-CYSTINE [-CSSCCSSCCSSC-] A NOVEL CROSS-LINKING MOTIF

The cysteine capped, ends protected cross linked motifs 6 and 7, arisi ng from pairs of proximally placed cysteines wherein within a 22 atom framework are inscribed 3 disulphide bridges and 2 peptide linkages, h ave been prepared and their conformations derived by detailed H-1 NMR studies and molecular modeling protocols, where excellent agreement wa s seen. Both compounds 6 and 7 possess a C-2 symmetric hydrogen bonded pair involving the peptide NH and the CO of the proximate N-protectin g group (Boc or Z). The nature of the latter profoundly influences the conformation. Thus, in 6 where the unit is Boc a bend conformation wa s promoted by hydrophobic interactions; alternatively in 7 with a Z-pr otecting group the conformation was linear. Compounds 6 and 7 have muc h promise in diverse aspects of protein design. Copyright (C) 1996 Els evier Science Ltd