Peptide bonding, deprotonated

One of the central mechanistic questions regarding ubiquitination has been whether the reaction utilizes general acid/base catalysis, possibly in a manner analogous to the catalysis of peptide-bond cleavage. For example, an acidic catalytic residue could deprotonate the substrate lysine and make it a better nucleophile for attacking the ubiquitin thioester bond. In addition, a basic catalytic residue could polarize the thioester bond making the carbonyl carbon a better electrophile, and... 

Then later in an aerobic world with mainly iron(III) both, zinc peptidases and iron oxygenases, evolved from these ancestors. Today nature mainly uses zinc centers in metalloenzymes for the hydrolyses of peptide bonds (99,J00). In the commonly accepted mechanism for zinc peptidases, zinc(II) has two tasks It polarizes the carbonyl functionality of the peptide bond that is going to be cleaved and it supports the deprotonation of the coordinated water nucleophile. 

The parameters that control epimerization in a peptide-bond-forming reaction can be assessed in terms of their thermodynamic and kinetic components. Thermodynamic effects are those that stabilize the deprotonated activated intermediate or the protonated tertiary amine. Kinetic effects are expressed based on the degree of steric hindrance between the tertiary amine and activated intermediate. Table 4 summarizes these contributions and shows examples of high, moderate, and low propensities for contribution to the intrinsic rate of racemization among the various parameters. 

DNA-Protein. A large number of proteins in nature perform their function by expediting electron transfer, and there is an extensive literature on electron transfer through proteins (see Refs. 122-124 for reviews). Relevant here are the observations that the excess electron has a large range (not readily trapped) [125] while the hole is relatively immobile (trapped by deprotonation at the peptide bond giving amido radicals) [126]. This raises the expectation that electrons but not holes could be transferred from protein to DNA. This has been observed by a number of groups [127-131]. 

Acid treatment 125) of [NiniH 3G4(H20)2] results in cleavage of the terminal Ni-N deprotonated peptide bond with a rate constant of 0.2 sec-1 at 25°C, faster than the corresponding rate for [Ni"H 3G4]2 Further dissociation of the tridentate tetraglycine ligand is much slower and the intermediate can be trapped by the addition of terpy to give a stable, six-coordinate nickel(III) mixed-ligand complex 126). It is notable that the calculated reduction potential for the mixed complex is lower than for either [NiIMH 3G4]- or for [NiMI(terpy)2]3 +. ... 

In summary, Cu(III) is stabilized by deprotonated peptide bonding, and this trivalent oxidation state is much more accessible in aqueous solution than had been realized. Variations in E° values of more than 500 mV occurs for CuIII,n redox couples as the nature of the coordinating groups change. If Cu(III) exists in nature, it is likely to be coordinated at least in part to deprotonated peptides, which play an important role in stabilizing this trivalent oxidation state. 

Studies of the rates of deamidation in a series of nonaqueous solvents have indicated a dependence of rate on the dielectric constant of the solvent. Although these experiments have generally involved solvents unsuitable for use in formulation, it is interesting to note a reported decrease of the rate of deamidation of N-terminal-blocked Boc-Asn-Gly-Gly in ethanol" (Boc = butoxycarbonyl). Similarly, the deamidation rate of the hexapeptide Val-Thr-Pro-Asn-Gly-Ala decreased with decrease in the dielectric constant of the solvent, an effect which was attributed to the destabilisation of the deprotonated peptide bond nitrogen anion which is involved in the formation of the cyclic imide intermediate. 

Numerous studies on the interactions of peptides and peptide-like ligands with vanadate have been reported.68,382 384>446>447 Some of these ligands coordinate through the carboxylate, the amine functionalities and the deprotonated amide nitrogen of the peptide bond,238,23 382 447 448 and some examples were described above in the section on polydentate ligands with two oxygen donor atoms. 

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