糖基转移酶在改善天然产物成药性方面的应用

Applications of glycosyltransferases in the improvement of druggability of natural products

天然产物结构新颖、生物活性多样,是药物或药物先导化合物的重要来源之一。但是,目前仅有极少数的天然产物被开发成药,生物活性不佳、溶解度低或稳定性差等是造成其成药性不佳的主要原因。鉴于天然产物结构的复杂性,通过化学结构修饰提高成药性受到了极大的挑战和限制,因此,更加多元化的酶法结构改造逐渐成为天然产物结构修饰的重要手段之一。由于选择性强、效率高、反应温和等优势,基于糖基转移酶的酶法糖基化修饰在改善天然产物成药性方面展现出了良好的应用前景。本文概述了糖基转移酶及其在天然产物结构修饰中的应用和挑战,可为天然产物的新药开发提供一定的参考和借鉴。

Natural products are one of the most important sources for druggable lead compounds given their diverse structures and activities.Nevertheless,very few of them can be directly developed to drugs.The undesirable druggability of natural products result from their weaker activity,lower aqueous solubility and poorer stability.Since improving druggability by chemical modifications is restricted by the limited access to the complex structures of natural products,enzymatic modification has gradually become one of important tools for the structural modification of natural products.Meanwhile,since enzymatic glycosylation by glycosyltransferases has shown certain advantages such as excellent regio-and stereo-selectivity,high catalytic efficiency and mild conditions.It has been a promising route for the improvement of druggability for natural products.In the present review,we summarize different glycosyltransferases and their application for structural modification of natural products as well as the challenges issues involved in the glycosylation,which provides a general perspective on the enzymatic modification of natural products for the improvement of their draggability.