S. M. Salam, Kensoh Kagawa, T. Matsubara
Dec 10, 2008
Citations
0
Influential Citations
18
Citations
Journal
Enzyme and Microbial Technology
Abstract
Abstract The kinetically controlled synthesis of N -benzyloxycarbonyl (Z)-dipeptides was investigated by the use of free amino acids as nucleophiles and a cysteine protease papain as catalyst. The coupling efficiency was significantly improved by the combined use of the carbamoylmethyl (Cam) ester of a Z-amino acid as acyl donor and frozen aqueous solution (ice, −16 or −24 °C) as reaction medium. The yield of peptide synthesis became high when both P 1 - and P ′ 1 -positions were occupied by small non-polar amino acids (Z-Gly-Gly-OH, 76%; Z-Gly-Ala-OH, 75%; Z-Ala-Ala-OH, 72%). Similar results were observed by the use of ficin as catalyst instead of papain. Furthermore, this strategy was applied to the papain-catalyzed incorporation of a d -configured amino acid such as d -alanine into the resulting peptides. Although the coupling in aqueous solution (30 °C) afforded the desired Z-dipeptides in low yields, the freezing of reaction medium reduced significantly unfavorable hydrolysis of the acyl donors, resulting in improvement of the coupling efficiency (Z-Gly- d -Ala-OH, 80%; Z-Ala- d -Ala-OH, 45%; Z- d -Ala-Ala-OH, 22%).