Papain-catalysed synthesis of dipeptides: a novel approach using free amino acids as nucleophiles.
For the first time, papain-catalysed synthesis of peptide bonds was successfully carried out using free amino acids as nucleophiles. In kinetically controlled experiments employing pH-Stat-mode, the ester substrates Z-Ala-OMe and Z-Gly-OMe were coupled with alanine, glutamine, and Cys(Acm)-OH, respectively. Under optimized reaction conditions (pH 9.2, high ratio nucleophile/carboxyl component, 10 mumol substrate mg-1 papain), the peptide yields ranged from 17% to 79%, depending on the structure of the amino and/or carboxyl component. The peptides formed were not hydrolysed under the chosen reaction conditions. With Z-Gly-OMe as the ester substrate, formation of the dipeptide was both rapid and high yielding. Papain-catalysed formation of peptide bonds applying free amino acids as nucleophiles might serve as an economic and easily manageable approach for the synthesis of short-chain peptides to be used in clinical nutrition.
Institute for Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, FRG.
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D000595:Amino Acid Sequence; D000596:Amino Acids; D004151:Dipeptides / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008969:Molecular Sequence Data; D010206:Papain / Q000378:metabolism*
D000596:Amino Acids; D004151:Dipeptides; D010206:Papain