title: Recent trends in protease-catalyzed peptide synthesis.
abstract: 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 cross-linked 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.
authors.affiliation: Laboratoire de Biochimie Analytique et Synthèse Bioorganique, UFR Chimie-Biochimie, Université Claude Bernard Lyon 1, 43 bd du 11 Novembre 1918, 69622 Villeurbanne Cedex France.
authors.forename: C
authors.initials: C
authors.lastname: Lombard
authors.forename: J
authors.initials: J
authors.lastname: Saulnier
authors.forename: J M
authors.initials: JM
authors.lastname: Wallach
mesh_terms: D000818:Animals; D002384:Catalysis; D004800:Enzymes, Immobilized / Q000378:metabolism; D006801:Humans; D018716:Molecular Mimicry; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D004800:Enzymes, Immobilized; D010455:Peptides; D010447:Peptide Hydrolases