Mechanism metal-peptide complexes

The kinetics and mechanisms of substitution reactions of metal complexes are discussed with emphasis on factors affecting the reactions of chelates and multidentate ligands. Evidence for associative mechanisms is reviewed. The substitution behavior of copper(III) and nickel(III) complexes is presented. Factors affecting the formation and dissociation rates of chelates are considered along with proton-transfer and nucleophilic substitution reactions of metal peptide complexes. The rate constants for the replacement of tripeptides from copper(II) by triethylene-... 

Figure 7-1 Activation of T cells by metal ions. Nickel and other metal ions appear to activate specific T cells by several different molecular mechanisms. (1) T cells with their T cell receptor respond to complexes of nickel with MHC-peptide similar to other hapten-peptide complexes. (2) Nickel forms a direct linker between MHC and the T cell receptor independent of the peptide with some similarities to superantigen-mediated T cell stimulation. (3) The processing of self peptides is disturbed by nickel resulting in cryptic self peptides presented to a T cell receptor.

The detailed structural study of metalloproteins was preceded by the study of small molecule metal complexes of amino adds and peptides [478]. The development of force fields for modeling metalloproteins might, logically, also begin with molecular mechanics modeling of amino acid and peptide complexes that have metal-ligand interactions of the type seen in the metalloprotein of interest. In this way, force-field... 

Feng WY, Gronert S, Fletcher KA, Warres A, Lebrilla CB. The mechanism of C-terminal fragments in alkali metal ion complexes of peptides. Int J Mass Spectrom. 2003 222 117-34. 

Bob s research interests and knowledge across chemistry were great. Throughout his career he retained an interest in biomimetic chemistry, specifically the study of metal ion-promoted reactions and reactions of molecules activated by metal ion coordination. His early interests in carbohydrate chemistry inspired him to study metal ion catalysis of both peptide formation and hydrolysis as well as studies in inorganic reaction mechanisms. He was particularly interested in the mechanisms of base-catalyzed hydrolysis within metal complexes and the development of the so-called dissociative conjugate-base (DCB) mechanism for base-catalyzed substitution reactions at inert d6 metal ions such as Co(III). 

Whilst metal-N(peptide) bond formation inhibits hydrolysis of the peptide bond, coordination to O(peptide) has the opposite effect. These differences in reactivity can be readily demonstrated and put to practical use with the inert Co111 complexes. One of the first examples was the reaction of [Co(trien)(H20)(OH)]2+ with peptides to give hydrolysis of the peptide bond at the N-terminal end. The proposed mechanism involving nucleophilic attack by hydroxide at the peptide carbon is shown in Scheme 7.110 Similar selective hydrolyses of N-terminal peptide bonds have since been demonstrated with other Co111 amine complexes and the reaction has been examined as a method for determining the N-terminal amino acid residue in peptides and proteins.1"112... 

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