title: A cyclodecapeptide ligand to vitamin B12.
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.
authors.affiliation: Département de Chimie Moléculaire-UMR-CNRS 5250 & ICMG FR 2607, Université Joseph Fourier, BP 51, 38041, Grenoble Cedex 9, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duléry
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Uhlich
authors.forename: Noélie
authors.initials: N
authors.lastname: Maillard
authors.forename: Viviana S
authors.initials: VS
authors.lastname: Fluxá
authors.forename: Julian
authors.initials: J
authors.lastname: Garcia
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Olivier
authors.initials: O
authors.lastname: Renaudet
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Reymond
authors.forename: Tamis
authors.initials: T
authors.lastname: Darbre
mesh_terms: D000595:Amino Acid Sequence; D003486:Cyanides / Q000378:metabolism; D015195:Drug Design; D007700:Kinetics; D008024:Ligands; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D003486:Cyanides; D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D014805:Vitamin B 12