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Hotoda’s Sequence and Anti-HIV Activity: Where Are We Now?

Department of Chemical Sciences, University of Napoli Federico II, Via Cintia 4, I-80126 Napoli, Italy
Authors to whom correspondence should be addressed.
Molecules 2019, 24(7), 1417;
Received: 7 March 2019 / Revised: 2 April 2019 / Accepted: 5 April 2019 / Published: 10 April 2019
(This article belongs to the Special Issue Recent Advances in the Development of Antiviral Agents)
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 (EC50 = 14 nM). View Full-Text
Keywords: anti-HIV agent; G-quadruplex; aptamer; Hotoda’s sequence; modified sequences anti-HIV agent; G-quadruplex; aptamer; Hotoda’s sequence; modified sequences
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Romanucci, V.; Zarrelli, A.; Di Fabio, G. Hotoda’s Sequence and Anti-HIV Activity: Where Are We Now? Molecules 2019, 24, 1417.

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