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Enantioselective reductive amination of [alpha]-keto acids by papain-based semisynthetic enzyme

机译:木瓜蛋白酶基半合成酶对α-酮酸的对映选择性还原胺化

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摘要

Alkylation of a cysteine residue in papain with a pyridoxamine (PX) cofactor was carried out. The resulting semisynthetic enzyme (papain-PX) has no detectable protease activity but has the ability to catalyze enantioselective reductive amination of α-keto acids. The conjugate was characterized by ion-exchange chromatography, and the optimal reaction conditions were found. We report that papain-PX reductively aminates the alkyl side chain of functionalized α-keto acids to give the respective α-amino acids with high enantioselectivities, greater than 70%. Based on these studies, we propose a new model for the catalytic activity of the semisynthetic enzyme with Interchem software. The results of the study demonstrate the effectiveness of the modified enzyme and its potential for engineering new catalytic specificity. [PUBLICATION ABSTRACT]
机译:木瓜蛋白酶中的半胱氨酸残基与吡ido胺(PX)辅助因子进行烷基化。所得的半合成酶(木瓜蛋白酶-PX)没有可检测的蛋白酶活性,但具有催化α-酮酸的对映选择性还原胺化的能力。通过离子交换色谱对偶联物进行表征,并确定了最佳反应条件。我们报道木瓜蛋白酶-PX还原胺化功能化的α-酮酸的烷基侧链,以给出具有高对映选择性(大于70%)的各个α-氨基酸。在这些研究的基础上,我们使用Interchem软件提出了一种半合成酶催化活性的新模型。研究结果证明了修饰酶的有效性及其在工程新催化特异性方面的潜力。 [出版物摘要]

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