Studies on enzymic peptide synthesis I.Synthesis of tryptophane analogue of Leu-enkephalin

来源 :Acta Chimica Sinica(English Edition) | 被引量 : 0次 | 上传用户:yangqun0215
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A tryptophane analogue of Leu-enkephalin,Tyr-Gly-Gly-Trp-Leu-NH_2,was synthesizedby stepwise elongation from C-terminal Leucylamide towards the N-terminal tyrosine using α-chy-motrypsin and papain catalysis.The selections of appropriate enzymes and suitable solvents werestudied.It was found that an N-blpcked amino acid ester served better as a donor than the cor-responding free amino acid in the peptide formation,irrespective of whether α-chymotrypsin or papainwas used,while,on the other hand,an N-blocked amino acid was needed as the donor in case ofthermolysin.In the last step of pentapeptide synthesis catalyzed by α-chymotrypsin,the phase transferprocess seems to be preferable to the homogeneous solution method.The results of this work showedsome advantages by the use of an immobilized enzyme.The tryptophane analogue of Leu-enke-phalin was also synthesized by the conventional organic method.Preliminary in vitro bioassayindicated that the synthetic Try-Gly-Gly-Try-Leu-NH_2 can inhibit the contraction of the guinea Pig’sileum caused by electric stimulation to nearly the same extent as the natural Leu-enkephalin does. A tryptophane analogue of Leu-enkephalin, Tyr-Gly-Gly-Trp-Leu-NH_2, was synthesized by stepwise elongation from C-terminal Leucylamide towards the N- terminal tyrosine using α-chy-motrypsin and papain catalysis. The selections of and suitable solvents were identified. It was found that an N-blpcked amino acid ester served better as a donor than the cor-responding free amino acid in the peptide formation, irrespective of whether α-chymotrypsin or papainwas used, while, on the other hand , an N-blocked amino acid was needed as the donor in case ofthermolysin.In the last step of pentapeptide synthesis catalyzed by α-chymotrypsin, the phase transferprocess seems to be preferable to the homogeneous solution method.The results of this work showedsome advantages by the use of an immobilized enzyme. The tryptophane analogue of Leu-enke-phalin was also synthesized by the conventional organic method. Preliminary in vitro bioassayedicated that the synthetic Try-Gly-Gly-Try-Leu-NH_2 can inhi bit the contraction of the guinea Pig’sileum caused by electric stimulation to nearly the same extent as the natural Leu-enkephalin does.
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