Peptide hydrolysis, selective

Peptide hydrolysis by platinum(II) (436) and palladium(II) complexes (437). In the latter case there is selective hydrolysis of the unactivated peptide bond in iV-acetylated L-histidylglycine the hydrolysis rate depends on the steric bulk of the catalyst. 

Thrombin [EC 3.4.21.5], also known as fibrinogenase, catalyzes the hydrolysis of peptide bonds, exhibiting preferential cleavage for the Arg—Gly peptide bond. The enzyme, a member of the peptidase family SI, activates fibrinogen to fibrin and releases fibrinopeptide A and B. Thrombin, formed from prothrombin, is more selective in peptide hydrolysis than trypsin or plasmin. 

Scheme 29 Selected transformations in the proposed mechanistic pathway for peptide hydrolysis by ApAP. The zinc-coordinated amino acid ligands are shown only on the resting state structure (left) for clarity.

High reaction rates at ambient temperatures and near neutral pH values are necessary to design artificial proteases applicable to food industries, catalytic turnover in the peptide hydrolysis, and hydrolysis of a broad range of protein substrates at selected sites. In addition, easy separation of the catalysts from protein hydrolysates is required. Construction of catalytic centers directly on immobile supports is, therefore, advantageous to designing artificial proteases applicable to protein industries. 

Since metal complexes with high activity for peptide hydrolysis were secured, it was subsequently attempted to achieve substrate selectivity in the hydrolysis of peptide bonds by the metal complexes. The active site of BB was constructed on the surface of partially chloromethylated cross-linked polystyrene (PCPS) (112). Here, the active site was chiral since L-arginine was used to introduce the guanidinium portion. 

Numerous examples of peptide hydrolysis have been achieved with the assistance of metal ions/metal complexes, including Zn, Co, Zr, Cu, Ni, Mo, Pd, and Pt. Detailed information can be found in a number of excellent and comprehensive review articles written on this subject [32—48]. According to the recognition mode, the site-selective peptide/protein degradation can be achieved in two ways a direct metal-peptide side chain interaction or a promoter s recognition site-peptide side chain interaction. 

In view of the requirement for metals in all cells, the optimum concentration for a virus may be different from that of the host cell and specific inhibition of the virus may occur by excess or deficiency of metal ion [3]. Certainly, regulation of inherent biological processes in this manner could produce selective antiviral effects. In a survey with various metal ions, zinc was the only one capable of inhibition of viral replication [39]. The mechanism of action is believed to be interference with the processing of viral polypeptides by inhibition of proteolytic cleavage [6]. The zinc may bind to the polypeptide and prevent the approach of the proteolytic enzyme [40]. Copper and nickel salts, interestingly, also inhibit peptide hydrolysis [41]. Zinc ions may also act on viral DNA polymerases [42,... 

Whereas acid catalyzed hydrolysis of peptides cleaves amide bonds indiscriminately and eventually breaks all of them enzymatic hydrolysis is much more selective and is the method used to convert a peptide into smaller fragments... 

Selective hydrolysis can be accomplished by using enzymes to catalyze cleavage at specific peptide bonds... 

Selective hydrolysis gave peptides having the following indicated sequences Phe Trp... 

Chymotrypsin (Section 27 10) A digestive enzyme that cat alyzes the hydrolysis of proteins Chymotrypsin selectively catalyzes the cleavage of the peptide bond between the car boxyl group of phenylalanine tyrosine or tryptophan and some other ammo acid... 

Selective cleavage of peptides and proteins is an important procedure in biochemistry and molecular biology. The half-life for the uncatalyzed hydrolysis of amide bonds is 350 500 years at room temperature and pH 4 8. Clearly, efficient methods of cleavage are needed. Despite their great catalytic power and selectivity to sequence, proteinases have some disadvantages. Peptides 420,423,424,426 an(j proteins428 429 can be hydrolytically cleaved near histidine and methionine residues with several palladium(II) aqua complexes, often with catalytic turnover. 

Acid- and base-sensitive lipidated peptides can be selectively deprotected by enzymatic hydrolysis of choline esters.[13al Choline esters of simple peptides, but also of sensitive peptide conjugates like phos-phorylated and glycosylated peptides,1141 nucleopep-tides1151 and lipidated peptides,113,1631 can be cleaved with acetyl choline esterase (AChE) and butyryl choline esterase (BChE) under virtually neutral conditions with complete chemoselectivity. Acid-labile farnesyl groups and base-sensitive thioesters are not attacked. 

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