The structurally unique "fleximer" nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor-ligand recognition and function. Recently they have been shown to have low-to-sub-micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex-bases) has been successfully coupled to both ribose and 2'-deoxyribose sugars by using the N-deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno-expanded tricyclic heterocyclic base, as well as several distal and proximal flex-bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.

中文翻译：

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通过近端和远端 Fleximer 碱基的酶促糖基化方便合成柔性核苷。

结构独特的“fleximer”核苷最初旨在研究核碱基的灵活性如何潜在地影响受体-配体识别和功能。最近，它们已被证明对多种病毒（包括冠状病毒、丝状病毒和黄病毒）具有低至亚微摩尔水平的活性。然而，迄今为止，特别是远端fleximers的合成非常繁琐且产量低。作为该问题的潜在解决方案，通过使用莱氏乳杆菌 (LlNDT) 和大肠杆菌嘌呤核苷的 N-脱氧核糖基转移酶 II，一系列近端 fleximer 碱基 (flex-bases) 已成功偶联到核糖和 2'-脱氧核糖上磷酸化酶 (PNP)。为了探索这种简便方法的范围，对噻吩扩展的三环杂环碱基以及几个远端和近端柔性碱基进行了转糖基化实验，以确定是否可以以这种方式获得相应的 fleximer 核苷，从而可能显着缩短这些具有生物学意义的化合物的途径。本文报道了这些研究的结果。