Peptides coordinating side chains

The binding of metal ions to peptides and proteins is a consequence of these molecules containing a great number of potential donor atoms through both the peptide backbone and amino acid side chains. The complexes formed exist in a variety of conformations that are sensitive to the pH environment of the complex [2,3]. With at least 20 amino acid combinations available, some with coordinating side chains, which can be linked in any particular order and length, the number of ligands that... 

The selectivity of peptide motifs for certain metals comes from the coordinating contribution from amino acid side chains, the common coordination number of the metal, hardness/softness of the metal ion, ligand field stabilisation effects and the hardness/softness of any coordinating side chains of the amino acid sequence. An example of the influence of side chains and the importance of the position of the side chain comes from the tripeptides Gly-Gly-His, also known as copper binding peptide. The side chain imidazole ring of the His residue has a very efficient nitrogen donor (the imidazole N), which can form a tetradentate chelate ring for coordination as in Scheme 10.3. 

Early studies on metal-peptide complexes were generally concerned with polyglycines, and there are several reviews on these complexes. In the first part of this article, we will discuss various metal-peptide complexes that have coordinating side chains. Comparison of these metal-peptide complexes will be made with their glycine analogs, and the differences will be noted. The second part of the article will deal with metal-mediated peptide-bond cleavage. 

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. 

Complexes of Peptides with Non-coordinating Side Chains. 286... 

Complexes of Peptides with Coordinating Side Chains. 287... 

In the case of the common peptides the comparison of the stability constants of zinc(II) and cadmium(II) complexes reveals the same trends as reported for the amino acids Favored complexation with zinc(II) in almost all cases, except for the thiolate ligands. The binding of several side chain residues may enhance the stability of cadmium(II) complexes but the extent of this stabihzation is relatively low. This is true even for the aspartyl or histidyl residues which are generally considered as the most strongly coordinating side chains in the corresponding... 

FIGURE 27 19 Proposed mechanism of hydrolysis of a peptide catalyzed by carboxypeptidase A The peptide is bound at the active site by an ionic bond between its C terminal ammo acid and the positively charged side chain of arginine 145 Coordination of Zn to oxygen makes the carbon of the carbonyl group more positive and increases the rate of nucleophilic attack by water... 

The N-terminal peptide fragment of des-angiotensinogen Val-Ile-His-Asn contains two strongly hydrophobic amino acid residues on the N-terminal site of His-3. The potentiometric data have shown that the NiH.2L complex with this albumin-like sequence is more than two orders of magnitude more stable than the respective complex with Gly-Gly-His.1744 The NMR-based molecular structure has shown that the side chains of Val-1 and lie-2 form a well-ordered hydrophobic fence (Figure 21) shielding one side of the coordination plane from the bulk of... 

Insertion of a thioamide (0[CSNH]) bond into a peptide backbone with noncoordinating side chains increases distinctly the coordination ability of the peptide toward Ni11. The thioamide sulfur is a much more potent donor than the carbonyl-O and it is a basic donor for Ni11 ion coordination around physiological pH.1764... 

Bacterial siderophores are typically small peptidic molecules, which contain side chains and functional groups that can provide high-affinity ligands for coordination of ferric ions. The structures of some siderophores are shown in Drechsel and Jung [142]. Siderophore synthesis occurs via enzymatic assembly by nonribosomal peptide synthetases [144], In bacteria, siderophore synthesis is... 

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