Potassium-induced loop conformational transition of a potent anti-HIV oligonucleotide

Journal of Biomolecular Structure & Dynamics
N JingM E Hogan

Abstract

Spectroscopic, thermal denaturation and kinetic studies have revealed that DNA oligonucleotides 5'-d(GGGTGGGTGGGTGGGT) (T30695) and 5'-d(GTGGTGGGTGGGTGGGT) (T30177) from extremely stable intramolecular G-tetrads via a two-step process that involves the binding of one K+ ion to a central pair of G-quartets and two additional K+ ions, presumably, to the loops (Jing et al., (1997) Biochemistry in press). In that these oligonucleotides are potent HIV-1 inhibitors and among the most active HIV-1 integrase inhibitors yet identified, we have sought to further characterize the K(+)-induced folding process for the purpose of rational chemical modification of these anti-HIV agents. Our NMR investigation demonstrates that in the presence of Li+ ions, T30695 forms an unimolecular tetrad fold, stabilized by a pair of syn-anti-syn-anti G-quartets comprising a central core. The NMR spectrum of T30695 as a function of K+ titration reveals a well-defined transition that saturates upon addition of three K+ ions per oligomer. During this process, the initial Li(+)-dependent G-quartet structure converts into a highly symmetrical, stable form (the NMR detected melting transition temperature is increased by approximately 20 degrees C). The conformat...Continue Reading

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Citations

Sep 17, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yongli GuanNaijie Jing
Jan 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Anh Tuân PhanDinshaw J Patel
Aug 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Adam Siddiqui-JainLaurence H Hurley
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Jun 28, 2016·Nucleic Acids Research·Colin G Wu, Maria Spies
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