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醛缩酶的立体选择性合成的最新进展。

Recent progress in stereoselective synthesis with aldolases.

机构信息

Biotransformation and Bioactive Molecules Group, Instituto de Química Avanzada de Cataluña, Consejo Superior de Investigaciones Científicas, Jordi Girona 18-26, 08034 Barcelona, Spain.

出版信息

Curr Opin Chem Biol. 2010 Apr;14(2):154-67. doi: 10.1016/j.cbpa.2009.11.029. Epub 2010 Jan 12.

DOI:10.1016/j.cbpa.2009.11.029
PMID:20071212
Abstract

Aldol reactions constitute a powerful methodology for carbon-carbon bond formation in synthetic organic chemistry. Biocatalysis by means of aldolases offers a unique stereoselective and green tool to perform this transformation. Recent advances in the field, fueled by either protein engineering or screening, greatly improved the number of synthetic opportunities from small chiral polyfunctional molecules to highly complex oligosaccharide analogs with potential pharmaceutical relevance. Furthermore, aldolases have been shown to be particularly valuable for obtaining new types of structures (i.e. generate molecular diversity) accessible for investigations in drug discovery. Extensive knowledge arising from biochemical studies and synthetic applications of natural aldolases has fostered the development of novel catalysts, such as the de novo computational design of aldolase enzymes, aldolase ribozymes, or synthetic peptides and foldamers with aldolase activity, outlining first steps toward the creation of tailor-made (bio)catalysts to suit any desired application.

摘要

Aldol 反应是合成有机化学中碳-碳键形成的一种强大方法。通过醛缩酶进行生物催化为进行这种转化提供了一种独特的立体选择性和绿色工具。最近在该领域的进展,无论是通过蛋白质工程还是筛选,都极大地增加了从小的手性多功能分子到具有潜在药物相关性的高度复杂寡糖类似物的合成机会。此外,醛缩酶已被证明对于获得新类型的结构(即产生分子多样性)特别有价值,这些结构可用于药物发现的研究。从天然醛缩酶的生化研究和合成应用中获得的广泛知识促进了新型催化剂的发展,例如醛缩酶酶的从头计算设计、醛缩酶核酶或具有醛缩酶活性的合成肽和折叠物,为创建定制(生物)催化剂以适应任何所需的应用勾勒出了第一步。

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