On the use of carboxamidomethyl esters in the protease-catalyzed peptide synthesis

Broadening of the substrate tolerance of α-chymotrypsin by using the carbamoylmethyl ester as an acyl donor in kinetically controlled peptide synthesis

“…2 As was expected, the yield of the desired peptide, as well as that of the hydrolysed donor ester, was extremely low even after 48 h when the methyl ester (Entry 1) was used as an acyl donor. This was also the case with other alkyl esters carrying a longer chain (Entries 2, 3,[5][6][7][8][9][10][11]. By contrast, when halogenated alkyl esters (Entries 12-15) were employed, the coupling efficiency was improved profoundly in accordance with our previous results.…”

“…9 It was later examined as a donor ester in the α-chymotrypsin-catalysed coupling of Z-or Boc-Phe conducted in aqueous organic media. 10 The chief concern at that time was to take advantage of the better solubility of this ester in the aqueous phase for the coupling of the α-chymotrypsin's good amino acid substrates. The superiority of the carbamoylmethyl ester can be seen from its reaction profile as compared with those of the other esters, e.g., the methyl and trifluoroethyl esters (Fig.…”

Proteases in Organic Synthesis

“…The next fragment (77−97) was used as Phe-NH 2 -modified carboxamido methyl ester. This special type of ester can be considered as fine-tuned analogues of unmodified carboxamido methyl esters which themselves have been used in other enzymatic syntheses . To prevent self-ligation, the N-terminus of the peptide fragment was blocked by the isonicotinyloxycarbonyl (iNoc) protecting group.…”

α-Chymotrypsin-catalyzed peptide synthesis in frozen aqueous solution using N-protected amino acid carbamoylmethyl esters as acyl donors

“…Previously, Jakubke et al 8 have found that carbamoylmethyl (Cam) ester of CBZ-Phe has a better solubility in an aqueous solution and is also a good acyl donor for a-chymotrypsin-catalyzed peptide synthesis. Recently, Miyazawa et al 9,10 have demonstrated the superiority of the Cam ester as the acyl donor for the a-chymotrypsin-catalyzed kinetically controlled peptide synthesis in acetonitrile with low content of water.…”