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Recent Trends in Protease-Catalyzed Peptide Synthesis

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Enzymatic peptide syntheses may be either thermodynamically- or kinetically-controlled. The former may be catalyzed by any proteases; the latter is limited to serine and cysteine proteases. This methodology is quite stereospecific and avoids side chain protection but is suffering of some drawbacks. Thus, only two industrial processes are by now developed: the production of aspartame and the conversion of porcine into human insulin. However, recent improvements have been carried out in different directions:

1-Search for proteases with high and/or new P'1 and P1 specificities.

2-Protease engineering to promote synthesis towards hydrolysis and to enlarge specificity.

3-Development of mimetic or "inverse" substrates to limit further hydrolysis of synthesized peptide. 4-Change of the physical state of reactants. Three axes have mainly be explored: solid-solid conversion, use of crosslinked enzyme crystals (CLEC) and enzyme immobilization. 5-Modification of experimental conditions. The principal and recent developments deal with: heterogeneous catalysis, synthesis in low water-containing organic solvents, in ionic liquids or at subzero temperatures. This review will illustrate these new orientations with examples described in the recent literature.
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Keywords: enzymatic peptide synthesis; protease; review

Document Type: Review Article

Affiliations: Laboratoire de Biochimie Analytique et Synthese Bioorganique, UFR Chimie-Biochimie, Universite Claude Bernard Lyon 1, 43 bd du 11 Novembre 1918, 69622 Villeurbanne Cedex France;

Publication date: 2005-10-01

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  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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