937801-72-4Relevant academic research and scientific papers
Copper-peptide complex structure and reactivity when found in conserved His-Xaa-His sequences
Park, Ga Young,Lee, Jung Yoon,Himes, Richard A.,Thomas, Gnana S.,Blackburn, Ninian J.,Karlin, Kenneth D.
supporting information, p. 12532 - 12535 (2014/12/11)
Oxygen-activating copper proteins may possess His-Xaa-His chelating sequences at their active sites and additionally exhibit imidiazole group δN vs εN tautomeric preferences. As shown here, such variations strongly affect copper ions coordination geometry, redox behavior, and oxidative reactivity. Copper(I) complexes bound to either δ-HGH or ε-HGH tripeptides were synthesized and characterized. Structural investigations using X-ray absorption spectroscopy, density functional theory calculations, and solution conductivity measurements reveal that δ-HGH forms the CuI dimer complex [{CuI(δ-HGH)}2]2+ (1) while ε-HGH binds CuI to give the monomeric complex [CuI(ε-HGH)]+ (2). Only 2 exhibits any reactivity, forming a strong CO adduct, [CuI(ε-HGH)(CO)]+, with properties closely matching those of the copper monooxygenase PHM. Also, 2 is reactive toward O2 or H2O2, giving a new type of O2-adduct or CuII-OOH complex, respectively.
Synthesis, physicochemical characterization, and biological activities of new carnosine derivatives stable in human serum as potential neuroprotective agents
Bertinaria, Massimo,Rolando, Barbara,Giorgis, Marta,Montanaro, Gabriele,Guglielmo, Stefano,Buonsanti, M. Federica,Carabelli, Valentina,Gavello, Daniela,Daniele, Pier Giuseppe,Fruttero, Roberta,Gasco, Alberto
experimental part, p. 611 - 621 (2011/03/20)
The synthesis and the physicochemical and biological characterization of a series of carnosine amides bearing on the amido group alkyl substituents endowed with different lipophilicity are described. All synthesized products display carnosine-like properties differentiating from the lead for their high serum stability. They are able to complex Cu2+ ions at physiological pH with the same stoichiometry as carnosine. The newly synthesized compounds display highly significant copper ion sequestering ability and are capable of protecting LDL from oxidation catalyzed by Cu2+ ions, the most active compounds being the most hydrophilic ones. All the synthesized amides show quite potent carnosine-like HNE quenching activity; in particular, 7d, the member of the series selected for this kind of study, is able to cross the blood-brain barrier (BBB) and to protect primary mouse hippocampal neurons against HNE-induced death. These products can be considered metabolically stable analogues of carnosine and are worthy of additional investigation as potential neuroprotective agents.
Synthesis and x-ray absorption spectroscopy structural studies of Cu(I) complexes of HistidylHistidine peptides: The predominance of linear 2-coordinate geometry
Himes, Richard A.,Ga, Young Park,Barry, Amanda N.,Blackburn, Ninian J.,Karlin, Kenneth D.
, p. 5352 - 5353 (2008/02/05)
Modified His-His dipeptides have been reacted with copper(I) salts to model active-site Cu ions bound by contiguous His residues in certain oxygen-activating copper proteins, as well as amyloid β-peptide. Chelation of copper(I) by these ligands affords linear, two-coordinate complexes as studied structurally by X-ray absorption spectroscopy. The complexes are robust toward oxidation, showing limited to no reactivity with O2, and they bind CO weakly. Reaction with a third ligand (N-methylimidazole) affords complexes with a markedly different structure (distorted T-shaped) and reactivity, binding CO and oxidizing rapidly upon exposure to dioxygen. Copyright
