A cyclodecapeptide ligand to vitamin B12 |
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Authors: | Duléry Vincent Uhlich Nicolas A Maillard Noélie Fluxá Viviana S Garcia Julian Dumy Pascal Renaudet Olivier Reymond Jean-Louis Darbre Tamis |
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Institution: | Département de Chimie Moléculaire-UMR-CNRS 5250 & ICMG FR 2607, Université Joseph Fourier, BP 51, 38041, Grenoble Cedex 9, France. |
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Abstract: | Libraries of cyclic decapeptides were screened with vitamin B(12) derivatives to give cyclic peptide ligands incorporating histidine and cysteine as coordinating residues and negatively charged amino acids. Two hits, cyclo-(HisAspGluProGlyIleAlaThrProdGln) and cyclo-(ValAspGluProGlyGluAspCysProdGln) were resynthesized in good yields for solution experiments. The peptides bind aquocobalamin with coordination of His or Cys to the cobalt with high affinities (K(a) approximately 10(5) M(-1)). Additional interactions between the peptide side chains and the vitamin B(12) corrin moiety were determined by studying the (1)H NMR solution 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. |
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