Cleavage of the peptide bond of beta-alanyl-L-histidine (carnosine) induced by a Co(III)-amine complexes: reaction, structure and mechanism.
Cleavage of the peptide bond occurs when beta]-alanyl-L-histidine (carnosine) reacts with [Co(tren)Cl2]+ (tren = tris(2-aminoethyl)amine) to give [Co(tren)(histidine)](2+) 1 and [Co(tren)(beta-alanine)](2+) 2. [Co(tren)(histidine)](2+) 1 crystallizes in the enantiomorphic space group P2(1)2(1)2(1) and 2 crystallizes in the P2(1)/c space group. The mechanism of the cleavage reactions were studied in detail for the precursor [Co(tren)Cl2]+ and [Co(trien)Cl2]+, which convert into [Co(tren)(OH)2]+/[Co(tren)(OH)(OH2)]2+ and [Co(trien)(OH)2]+/[Co(trien)(OH)(OH2)]2+ in water at basic pH (trien = 1,4,7,10-tetraazadecane). At a slightly basic pH, the initial coordination of the substrate (beta-alanyl-L-histidine) is by the carboxylate group for the reaction with [Co(tren)Cl2]+. This is followed by a rate-limiting nucleophilic attack of the hydroxide group at the beta-alanyl-L-histidine carbonyl group. In a strongly basic reaction medium substrate, binding of the metal was through carboxylate and amine terminals. On the other hand, for the reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine, the initial coordination of the substrate takes place via an imidazole ring nitrogen, independently, and followed by a nucleophilic attack of the hydroxide group at the beta-alanyl-L-histidine carbonyl group. The circular dichroism spectrum for 1 suggests that a very small extent of racemization of the amino acid (L-histidine) takes place during the cleavage reaction between [Co(tren)Cl2]+ and beta-alanyl-L-histidine. Reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine also causes cleavage of the peptide bond, producing a free beta-alanyl molecule and a cationic fragment [cis-alpha-Co(trien)(histidine)](2+) 3 that crystallizes in the optically active space group P2(1)2(1)2(1). Unlike the previous case an appreciable degree of racemization of the L-histidine takes place during the reaction between [cis-beta-Co(trien)Cl2]+ and beta-alanyl-L-histidine. Crystals containing L-histidine and D-histidine fragments in the [cis-alpha-Co(trien)(histidine)]2+ moiety were crystallographically documented by mounting a number of randomly selected crystals.
Saha
Manas K
MK
Department of Chemistry, University of Houston, Houston, Texas 77204, USA.
Mukhopadhyay
Uday
U
Bernal
Ivan
I
D000409:Alanine / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D002336:Carnosine / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006639:Histidine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D000588:Amines; D009942:Organometallic Compounds; D006639:Histidine; D003300:Copper; D002336:Carnosine; D000409:Alanine