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兰德霉素的化学与生物学,一类不断扩展的聚酮类天然产物家族

Chemistry and biology of landomycins, an expanding family of polyketide natural products.

作者信息

Ostash B, Korynevska A, Stoika R, Fedorenko V

机构信息

Department of Genetics and Biotechnology, Ivan Franko National University of L'viv, L'viv 79005, Ukraine.

出版信息

Mini Rev Med Chem. 2009 Aug;9(9):1040-51. doi: 10.2174/138955709788922593.

Abstract

This review covers existing literature (from 1990 to 2008) on landomycins (LS), a family of glycosylated angucyclines, with an emphasis on the bioactivity scope of landomycin (La)-like structures accessible via biocombinatorial manipulations. Some LS display strong antitumor activity and have inspired several chemical studies focused mainly on their unusual deoxysugar chains. A decade of genetic studies on La-producing bacteria has provided many novel molecules with altered structure and activity. A complex nonlinear correlation between the length of the carbohydrate tail of LS and their antitumor activity has also been revealed. It implies that simpler LS than the largest member of the family, LaA, are still potential drug leads. Combinatorial biosynthesis appears to be a powerful tool to search the chemical space around the La scaffold.

摘要

本综述涵盖了1990年至2008年关于地霉素(LS)的现有文献,地霉素是一类糖基化的安古霉素,重点关注通过生物组合操作可获得的类地霉素(La)结构的生物活性范围。一些地霉素显示出强大的抗肿瘤活性,并激发了几项主要集中在其异常脱氧糖链上的化学研究。对产生La的细菌进行的十年遗传学研究提供了许多结构和活性改变的新分子。还揭示了地霉素碳水化合物尾部长度与其抗肿瘤活性之间复杂的非线性关系。这意味着比该家族最大成员LaA更简单的地霉素仍是潜在的药物先导物。组合生物合成似乎是探索La支架周围化学空间的有力工具。

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