Peptide bonds, cleavage

Figure 28.19 The cleavage reaction of FeBABE involves a catalytic process using peroxide and ascorbate to form reactive oxygen species. Any protein structure in the immediate vicinity of the FeBABE label on the bait protein will undergo peptide bond cleavage.

As mentioned earlier, by far the largest number of zinc enzymes are involved in hydrolytic reactions, frequently associated with peptide bond cleavage. Carboxypeptidases and ther-molysins are, respectively, exopeptidases, which remove amino acids from the carboxyl terminus of proteins, and endopeptidases, which cleave peptide bonds in the interior of a polypeptide chain. However, they both have almost identical active sites (Figure 12.4) with two His and one Glu ligands to the Zn2+. It appears that the Glu residue can be bound in a mono- or bi-dentate manner. The two classes of enzymes are expected to follow similar reaction mechanisms. 

Besides the specific reactions discussed in the previous and subsequent sections, degradation studies often reveal that peptide bond cleavage can occur at unexpected sites (see, e.g., the unlabeled reactions in Figs. 6.17 and 6.21). Future investigations will certainly expand our understanding of lability factors in peptides. 

Y. Nabuchi, E. Fujiwara, H. Kuboniwa, Y. Asoh, H. Ushio, The Stability and Degradation Pathway of Recombinant Human Parathyroid Hormone Deamidation of Asparaginyl Residue and Peptide Bond Cleavage at Aspartyl and Asparaginyl Residues , Pharm. Res. 1997, 14, 1685-1690. 

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... 

Since then, catalytic antibodies which catalyze different chemical reactions have been described. The reactions range from ester or carbonate hydrolysis to carbon-carbon bond forming reactions, bimolecular amide formation or peptide bond cleavage, so the application of catalytic antibodies to general synthetic organic chemistry seems to be very promising [22]. 

Posttranslational modifications can be broken down into two main classes those that are reversible and those that are irreversible. Included in the large group of reversible posttranslational modifications are phosphorylation, acetylation, and disulfide formation. Irreversible posttranslational modifications include peptide bond cleavage as in intein splicing also irreversible is the introduction of a phosphopantetheinyl group during fatty acid, polyketide, and nonribosomal peptide biosyntheses. The current debate is whether to classify lysine N-methylation as reversible or irreversible. Recently, there have been reports of lysine demethylases. ... 

Proteases, since their discovery, have played an important role in both basic and applied research because their sometimes exquisite selectivity of peptide bond cleavage can be extremely useful in the elucidation of other proteins structures and function. The following three sub-sections give several examples of how proteases are used in specific aspects of research. 

Scheme 3 Schematic Route for Determination of Disulfide Topologies by Differentiated Alkylation of Partially Reduced Disulfides and/or Peptide Bond Cleavage by the Cyanylation MethodI46-561...

Residues furnishing the primary recognition point for the protease or reagent peptide bond cleavage occurs on either the carbonyl (C) or the amino (N) side of the indicated amino acid... 

Arginine residues are very resistant to most of the usual reagents used for chemical modification. King (166) has reported the conversion of these residues to S-N- (2-pyrimidinyl) ornithine by treatment with malonaldehyde in 10 N HC1. Essentially complete modification of the 4 arginine residues in RNase was obtained. Peptide bond cleavage and disulfide interchange also occurred, however, and no conclusions are warranted on the relation of the properties of the product to the actual arginine modification. 

Ardo, Y. and Meisel, H. (1991). Methods for direct measurement of peptide bond cleavage in cheese. Bull. Int. Dairy Fed. 261,10-13. 

Wu, C. Y., Chen, S. T., Chiou, S. H., and Wang, K. T. 1992. Specific peptide-bond cleavage by microwave irradiation in weak acid solution. J. Protein Chem. 77 45-50. 

Preparation of freeze dried p-anisoyl streptokinase/plasminogen complex without internal peptide bond cleavages ... 

As a consequence of dehydroalanine and B-methyldehydroalanine formation specific bond cleavage can occur. Ebert et al. (56) have shown that addition of cysteine to the double bonds of polydehydroalanine and copolymers of dehydroalanine results in increased solubility and decrease in molecular weight because of peptide bond cleavage caused by formation of a thiazolidine. 

This reaction can be used for selective peptide chain cleavage of cysteine-containing polypeptides and proteins under rather mild conditions. Mild acid treatment of dehydroalanine-containing polypeptides and proteins leads to specific peptide bond cleavage with formation of pyruvate and ammonia (57-59)). 

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. 

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