Remarkable effects of donor esters on the α-chymotrypsin-catalyzed couplings of inherently poor amino acid substrates

Tetrahedron Letters

Volumn 39, Issue 9, 1998, Pages 997-1000

  Miyazawa, Toshifumi ^a   Tanaka, Kayoko ^a   Ensatsu, Eiichi ^a   Yanagihara, Ryoji ^a   Yamada, Takashi ^a  

^a KONAN UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; AMINO ACID; CHYMOTRYPSIN A; ESTER;

ARTICLE; CHEMICAL REACTION; POLYMERIZATION; PROTEIN SYNTHESIS; TECHNIQUE;

EID: 0032568065     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)10798-5     Document Type: Article

References (12)

1. 1. a) C.-H. Wong and G. M. Whitesides, Enzymes in Synthetic Organic Chemistry, Pergamon, Oxford, 1994, p. 46;
2. b) H.-D. Jakubke, Enzyme Catalysis in Organic Synthesis, eds. K. Drauz and H. Waldmann, VCH, Weinheim, 1995, B.2.5 (p. 431).
3. 2. T. Miyazawa, S. Nakajo, M. Nishikawa, K. Imagawa, R. Yanagihara and T. Yamada, J. Chem. Soc., Perkin Trans. 1, 1996, 1214.
4. 3. W. Kullmann, Enzymatic Peptide Synthesis, CRC Press, Boca Raton, 1987, p. 41.
5. 4. The abbreviations given by the IUPAC-IUB Commission are used throughout. Additional abbreviations: Z, benzyloxycarbonyl; Tris, tris(hydroxymethyl)aminomethane; TEA, triethylamine; Phe(2Cl), 2-chlorophenylalanine; Phe(2Br), 2-bromophenylalanine; Boc, t-butoxycarbonyl.
6. 4 as the eluent.
7. 3, 0.1.
8. 7. In the kinetically controlled approach of protease-catalyzed peptide synthesis, the acyl-enzyme intermediate is partitioned between aminolysis and hydrolysis, affording the peptide product and the hydrolysis product of the donor ester. Once the acyl-enzyme intermediate is formed, its competitive partitioning is supposed to be unaffected by the ester moiety of the acyl donor, according to the simplified reaction scheme. It may have some effect in the case when the leaving alkoxy group (OR) is not completely detached from the acyl-enzyme intermediate before the deacylation by the nucleophiles occurs.
9. 8. This ester was proposed as an active ester for the conventional peptide synthesis a long time ago: R. Schwyzer, B. Iselin, W. Rittel and P. Sieber, Helv. Chim. Acta, 1956, 39, 872.
10. 9. The use of carbamoylmethyl esters as enzyme substrates was reported some decades ago: R. J. Kerr and C. Niemann, J. Org. Chem., 1958, 23, 304. The carbamoylmethyl ester was also examined as a donor ester in the α-chymotrypsin-catalyzed coupling of Z-or Boc-phenylalanine in aqueous organic media, mainly taking advantage of its better solubility in aqueous phase: P. Kuhl, U. Zacharias, H. Burckhardt and H.-D. Jakubke, Monatsh. Chem., 1986, 117, 1195.
11. 9. The use of carbamoylmethyl esters as enzyme substrates was reported some decades ago: R. J. Kerr and C. Niemann, J. Org. Chem., 1958, 23, 304. The carbamoylmethyl ester was also examined as a donor ester in the α-chymotrypsin-catalyzed coupling of Z-or Boc-phenylalanine in aqueous organic media, mainly taking advantage of its better solubility in aqueous phase: P. Kuhl, U. Zacharias, H. Burckhardt and H.-D. Jakubke, Monatsh. Chem., 1986, 117, 1195.
12. 10. R. W. Taft, Jr., Steric Effects in Organic Chemistry, ed. M. S. Newman, John Wiely, New York, 1956, Chap. 13.