Department of Chemical Sciences, University of Napoli Federico II, Via Cintia 4, I-80126 Napoli, Italy.
Molecules. 2019 Apr 10;24(7):1417. doi: 10.3390/molecules24071417.
The pharmacological relevance of ODNs forming G-quadruplexes as anti-HIV agents has been extensively reported in the literature over the last few years. Recent detailed studies have elucidated the peculiar arrangement adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. In this review, we have reported the history of a strong anti-HIV agent: the 6-mer d(TGGGAG) sequence, commonly called "Hotoda's sequence". In particular, all findings reported on this sequence and its modified sequences have been discussed considering the following research phases: (i) discovery of the first 5'-modified active d(TGGGAG) sequences; (ii) synthesis of a variety of end-modified d(TGGGAG) sequences; (iii) biophysical and NMR investigations of natural and modified Hotoda's sequences; (iv); kinetic studies on the most active 5'-modified d(TGGGAG) sequences; and (v) extensive anti-HIV screening of G-quadruplexes formed by d(TGGGAG) sequences. This review aims to clarify all results obtained over the years on Hotoda's sequence, revealing its potentiality as a strong anti-HIV agent (EC = 14 nM).
近年来，文献中广泛报道了寡核苷酸形成 G-四链体作为抗 HIV 药物的药理学相关性。最近的详细研究阐明了许多基于 G-四链体的适体所采用的特殊排列方式，并提供了它们作用机制的深入了解。在这篇综述中，我们报告了一种强大的抗 HIV 药物的历史：6- mer d(TGGGAG) 序列，通常称为“Hotoda 序列”。特别是，考虑到以下研究阶段，讨论了关于该序列及其修饰序列的所有发现：(i) 发现第一个 5'- 修饰的活性 d(TGGGAG) 序列；(ii) 各种末端修饰的 d(TGGGAG) 序列的合成；(iii) 天然和修饰的 Hotoda 序列的生物物理和 NMR 研究；(iv) 最活跃的 5'- 修饰的 d(TGGGAG) 序列的动力学研究；以及 (v) d(TGGGAG) 序列形成的 G-四链体的广泛抗 HIV 筛选。本综述旨在澄清多年来在 Hotoda 序列上获得的所有结果，揭示其作为一种强大的抗 HIV 药物（EC = 14 nM）的潜力。
