Transition metals peptide hydrolysis

For the mechanism of azolide hydrolysis under specific conditions like, for example, in micelles,[24] in the presence of cycloamyloses,[25] or transition metals,[26] see the references noted and the literature cited therein. Thorough investigation of the hydrolysis of azolides is certainly important for studying the reactivity of those compounds in chemical and biochemical systems.[27] On the other hand, from the point of view of synthetic chemistry, interest is centred instead on die potential for chemical transformations e.g., alcoholysis to esters, aminolysis to amides or peptides, acylation of carboxylic acids to anhydrides and of peroxides to peroxycarboxylic acids, as well as certain C-acylations and a variety of other preparative applications. 

One possible way to prevent transition metal ions from precipitating, and thus allow them to coordinate to peptides, is to have a primary ligating site or anchor, which would allow the amide oxygen to chelate to the metal. This will allow for subsequent substitution of the amide hydrogen by the metal ion. This primary binding site reduces the importance of metal ion hydrolysis and permits attainment of pH values where substitution of a metal ion for an amide hydrogen may occur (equation 3). 

The active site of methionine aminopeptidase contains a binuclear cobalt complex that is required for activity, although a number of divalent metal ions support turnover to varying degrees. X-ray crystallographic studies on the enzyme in complexes with transition state analogs suggests that the binuclear metal cluster serves to stabilize the tetrahedral intermediate in peptide hydrolysis. ... 

Remarkably, the dynamic peptide library is also self-selecting because differential bonding of its members as ligands to transition metal centers causes differential stabilization against hydrolysis. It means a self-selection of stable metallo-peptide structures. 

The Ce + ion is one of the most active catalysts for peptide hydrolysis. Its activity is much higher than that of the trivalent lanthanide ions and other transition metal ions. In particular, Ce + is far superior to other tetravalent ions like Zr" or Hf +. Yashiro et al. (1994) reported that dipeptides and tripeptides were efficiently hydrolyzed under neutral conditions by the y-cyclodextrin complex of cerium(IV). Komiyama and coworkers (Takarada et al., 2000) studied the catalytic hydrolysis of oligopeptides by cerium(IV) salts. The hydrolysis is fast, especially when the oligopeptides contain no metal-coordinating side-chains. The hydrolysis rates of the dipeptides, tripeptides and tetrapeptides is similar. The hydrolysis reaction was performed at pH 7 and 50 °C and under these conditions, the half-life of the amide bond was only a few hours. The authors found that ammonium hexanitratocerate(IV) is more active than other cerium(IV) compounds like ammonium cerium(IV) sulfate, cerium(IV) sulfate and cerium(IV) hydroxide. The lower reactivity of ammonium cerium(IV) sulfate is ascribed to the competitive inhibition by sulfate ions, while the low reactivity of cerium(IV) sulfate and cerium(IV) hydroxide can be explained by their poor solubility in water. However, in the reaction mixtures at the given reaction conditions, most of the cerium(IV) consists in a gel of cerium(IV) hydroxides. No oxidative cleavage has been observed. 

Chelates with amino acids or low molecular peptides may be regarded either from the standpoint of the metal ion or from the ligand. Thus, amino acid absorption and especially the transport of metal ions are substantially facilitated. This has been elucidated for transition ions which are biochemically important but tend to form macromolecular aquo-hydroxo-complexes. These complexes have a molecular weight too high to be absorbed directly. If these metal ions are prevented from hydrolysis by complexing with low molecular weight peptides they can be much better transported to their metabolic site. 

---