Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
PLoS One. 2021 Oct 14;16(10):e0257623. doi: 10.1371/journal.pone.0257623. eCollection 2021.
Fucosyltransferase 2 (FUT2) catalyzes the biosynthesis of A, B, and H antigens and other important glycans, such as (Sialyl Lewisx) sLex, and (Sialyl Lewisy) sLey. The production of these glycans is increased in various cancers, hence to design and develop specific inhibitors of FUT2 is a therapeutic strategy. The current study was designed to identify the inhibitors for FUT2. In silico screening of 300 synthetic compounds was performed. Molecular docking studies highlighted the interactions of ligands with critical amino acid residues, present in the active site of FUT2. The epitope mapping in ligands was performed using the STD-NMR experiments to identify the interactions between ligands, and receptor protein. Finally, we have identified 5 lead compounds 4, 5, 26, 27, and 28 that can be studied for further development as cancer therapeutic agents.
岩藻糖基转移酶 2（FUT2）催化 A、B 和 H 抗原和其他重要聚糖的生物合成，如（唾液酸化 Lewisx）sLex 和（唾液酸化 Lewisy）sLey。这些聚糖的产生在各种癌症中增加，因此设计和开发 FUT2 的特异性抑制剂是一种治疗策略。本研究旨在鉴定 FUT2 的抑制剂。对 300 种合成化合物进行了计算机筛选。分子对接研究突出了配体与 FUT2 活性部位中关键氨基酸残基的相互作用。使用 STD-NMR 实验进行配体的表位作图，以确定配体与受体蛋白之间的相互作用。最后，我们确定了 5 个先导化合物 4、5、26、27 和 28，它们可以作为癌症治疗剂进一步研究。
