Goel Bharat, Tripathi Nancy, Mukherjee Debaraj, Jain Shreyans K
Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, Uttar Pradesh, India.
Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India.
Eur J Med Chem. 2021 Mar 5;213:113156. doi: 10.1016/j.ejmech.2021.113156. Epub 2021 Jan 9.
Glycorandomization is a natural product derivatization strategy in which different sugar moieties are linked to the aglycone part of the naturally existing glycosides to create glycorandomized libraries. Sugars attached to the natural products are responsible for affecting their solubility, mechanism of action, target recognition, and toxicity and thus, by changing the sugar part, these properties could be modified. Glycorandomization can be done via two approaches (i) a synthetic approach known as neoglycorandomization, and (ii) chemoenzymatic approach including in-vitro and in-vivo glycorandomization. Glycorandomization can be a promising technology for the drug discovery that has proved its potential to improve pharmacokinetic (solubility) and pharmacodynamic profile (mechanism of action, toxicity, and target recognition) of the parent compounds. The substrate flexibility of glycosyltransferases and other enzymes towards sugars and/or aglycone substrates has made this technique versatile. Further, the enzymes can be altered by genetic engineering to generate glycorandomized libraries of diverse natural product scaffolds. This technique has the potential to produce new compounds that can be helpful to the mankind by treating the threatening disease states. This review covers the different strategies for glycorandomization as a tool in drug discovery and development. The fundamentals of glycorandomization, different types, and further development of differentially glycorandomized libraries of natural products and small molecule based drugs have been discussed.
糖基随机化是一种天然产物衍生化策略，其中不同的糖部分与天然存在的糖苷的苷元部分相连，以创建糖基随机化文库。连接到天然产物上的糖负责影响其溶解度、作用机制、靶点识别和毒性，因此，通过改变糖部分，可以改变这些性质。糖基随机化可以通过两种方法实现：（i）一种称为新糖基随机化的合成方法，以及（ii）包括体外和体内糖基随机化的化学酶法。糖基随机化可能是一种有前途的药物发现技术，已证明其有潜力改善母体化合物的药代动力学（溶解度）和药效学特征（作用机制、毒性和靶点识别）。糖基转移酶和其他酶对糖和/或苷元底物的底物灵活性使该技术具有通用性。此外，可以通过基因工程改变酶，以生成各种天然产物支架的糖基随机化文库。该技术有可能产生有助于人类治疗威胁性疾病状态的新化合物。本综述涵盖了糖基随机化作为药物发现和开发工具的不同策略。讨论了糖基随机化的基本原理、不同类型以及天然产物和基于小分子的药物的差异糖基随机化文库的进一步发展。
