Département de chimie moléculaire

Libraries of cyclic decapeptides were screened with vitamin B12 derivs. to give cyclic peptide ligands incorporating histidine and cysteine as coordinating residues and neg. charged amino acids. Two hits, cyclo(His-Asp-Glu-Pro-Gly-Ile-Ala-Thr-Pro-D-Gln) and cyclo(Val-Asp-Glu-Pro-Gly-Glu-Asp-Cys-Pro-D-Gln) were resynthesized in good yields for soln. expts. The peptides bind aquocobalamin with coordination of His or Cys to the cobalt with high affinities (Ka ∼ 105 M-1). Addnl. interactions between the peptide side chains and the vitamin B12 corrin moiety were detd. by studying the 1H NMR soln. structure. The cyclopeptide-cobalamin complex with the histidine residue showed enhanced stability towards cyanide exchange, demonstrating the shielding effect of the ligand on the metal center. [on SciFinder(R)]