The reactivity of N-coordinated amides in metallopeptide frameworks: molecular events in metal-induced pathogenic pathways?
The amino acid derived tertiary amide ligand tert-butoxycarbonyl-(S)-alanine-N,N-bis(picolyl)amide (Boc-(S)-Ala-bpa, 1) has been synthesized as a model for metal-coordinating peptide frameworks. Its reactions with copper(II) and cadmium(II) salts have been studied. Binding of Cu2+ results in amide bond cleavage and formation of [(bpa)(solvent)Cu]2+ complexes. In contrast, the stable, eight-coordinate complex [(Boc-(S)-Ala-bpa)Cd(NO3)2] (5) has been isolated and characterized by X-ray crystallography. An unusual tertiary amide nitrogen coordination is observed in 5; this gives rise to significantly reduced cis-trans isomerization barriers. Possible implications for metal-induced conformational changes in proteins are discussed.
Niklas
N
N
Institute of Inorganic Chemistry, University of Erlangen Germany.
Hampel
F
F
Liehr
G
G
Zahl
A
A
Alsfasser
R
R
D000577:Amides / Q000737:chemistry*; D002104:Cadmium / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D019216:Metals, Heavy / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects
D000577:Amides; D019216:Metals, Heavy; D010455:Peptides; D002104:Cadmium; D003300:Copper