Peptides catalytic 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.

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]. 

A more useful application of the electron-attracting effect of aryl subtituents is found in the cleavage of 4-picolyl derivatives of protected cysteine and tyrosine in peptide synthesis (Scheme 14).Catalytic cleavage of these derivatives is usually unattractive for SProtecting groups removable also include 3- and 4-picolyl esters. ... 

In recent years, methods for the catalytic cleavage of the P-O bond in phosphate esters have been developed. It is now reported that a cyclic P-sheet peptide -based binuclear zinc (II) complex markedly accelerated the cleavage of the phosphodiester linkage of the RNA model substrate 2-hydroxypropyl p-nitro-phenyl phosphate (102) (Scheme 17). °... 

As a first example, the cysteine proteinase, papain, was studied in its catalytic cleavage of peptide substrates. The enzyme contains over 200 residues, and the particular mechanism that has been proposed by Drenth, et al (109) was chosen for examination. 

Figure 9 Serine hydrolases as targets of ABPP. (a) Catalytic mechanism of peptide substrate cleavage via the action of a catalytic triad, (b) Aryl phosphonate and fluorophosphonate probe scaffolds.

The signal sequence is proteoly tically cleaved by signal pepetidase (member enzyme of translocon) once protein is translocated. The eukaryotic signal peptidases have multiple catalytic subunits with broad substrate specificity. The enzyme generally cleaves at a site that has small aliphatic residues at position -1 and -3. On-line prediction of signal peptide and cleavage site is available at PrediSi (http //www.predisi.de). 

The carboxypeptidase A, mainly isolated from bovine pancreas, is a metalloprotease that hydrolyzes peptide linkages. Particularly, the catalytic cleavage of the peptide in the presence of the enzyme preferably occurs at the C-terminal amide bond with a large hydrophobic amino acid side chain, such as phenylalanine, because the enzyme has a steady binding pocket for an aromatic ring. A proposed mechanism of initial step is shown in Fig. 2 The zinc ion is coordinated by two histidines, one chelating (rj —)glutamate and one water molecule. 

Figure 12.3 Peptide vinyl sulfones and peptide epoxyketones in activity-based proteasome profiling, (a) Catalytic mechanism of proteasome-mediated peptide bond cleavage, (b) Covalent adducts of protea-somes reacting with vinyl sulfones and...

W. W. Bachovchin and J. D. Roberts (1978), Nitrogen-15 nuclear magnetic resonance spectroscopy. The state of histidine in the catalytic triad of a-lytic protease. Implications for the charge-relay mechanism of peptide bond cleavage by serine proteases. J. Amer. Chem. Soc. 100, 8041-8047. 

The protected materials have been of particular value in peptide chemistry. Cleavage of esters (2) takes place not only under the more obvious aqueous alkali or catalytic hydrogenation conditions, but also with Sodium-Ammonia or by electrolytic reduc-... 

Parallel to these metal/metal oxide force-field development efforts, we also extended the first- and second-row elements that can incorporate the water description provided here. These extensions include carbon and nitrogen, in a ReaxFF description for glycine reactions in water, sulfur, related to the catalytic cleavage of S-S bridges, and phosphates. Recently, we have merged the ReaxFF glycine description with a recently developed parameter set for titania/water interactions, enabling reactive simulations of peptides on titania surfaces. ... 

Serine proteinases such as chymotrypsin and subtilisin catalyze the cleavage of peptide bonds. Four features essential for catalysis are present in the three-dimensional structures of all serine proteinases a catalytic triad, an oxyanion binding site, a substrate specificity pocket, and a nonspecific binding site for polypeptide substrates. These four features, in a very similar arrangement, are present in both chymotrypsin and subtilisin even though they are achieved in the two enzymes in completely different ways by quite different three-dimensional structures. Chymotrypsin is built up from two p-barrel domains, whereas the subtilisin structure is of the a/p type. These two enzymes provide an example of convergent evolution where completely different loop regions, attached to different framework structures, form similar active sites. 

As we have already seen zinc-finger peptides are well-studied polypeptide motifs that have found many applications in synthetic systems, mostly because of their abihty to bind metal ions and interact with oligonucleotides. In this context the report by lima and Crooke [44] of the hydrolytic cleavage by a zinc-finger peptide devoid of any metal ion is a surprising. The system they studied, a 30-amino acid sequence, is based on a catalytic mechanism very similar to that discussed above... 

Several classes of non-covalent substrate based inhibitors have been reported, and are grouped below based on the nature of the C-terminal group interacting with the catalytic triad of the enzyme. The majority of the reported inhibitors are based on the N-terminal product of a modified substrate of the NS5A/5B cleavage side or to a lesser extent of the NS4A/4B substrate peptide. 

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