Kinetic ESI-MS Studies of Potent Anti-HIV Aptamers Based on the G-Quadruplex Forming Sequence d(TGGGAG)

Valeria Romanucci; Adrien Marchand; Oscar Mendoza; Daniele D'Alonzo; Armando Zarrelli; Valérie Gabelica; Giovanni Di Fabio

doi:10.1021/acsmedchemlett.5b00408

Kinetic ESI-MS Studies of Potent Anti-HIV Aptamers Based on the G-Quadruplex Forming Sequence d(TGGGAG)

ACS Med Chem Lett. 2016 Jan 26;7(3):256-60. doi: 10.1021/acsmedchemlett.5b00408. eCollection 2016 Mar 10.

Authors

Valeria Romanucci¹, Adrien Marchand², Oscar Mendoza², Daniele D'Alonzo¹, Armando Zarrelli¹, Valérie Gabelica², Giovanni Di Fabio¹

Affiliations

¹ Department of Chemical Sciences, University of Napoli Federico II , Via Cintia, I-80126 Napoli, Italy.
² IECB, ARNA Laboratory, University of Bordeaux, 33600 Pessac, France; Inserm, U869, ARNA Laboratory, Institut National de la Santé et de la Recherche Médicale, 33000 Bordeaux, France.

Abstract

To investigate what properties make tetramolecular G-quadruplex ODNs good anti-HIV aptamers, we studied the stoichiometry and the self-assembly kinetics of the highly active 5'-end modified G-quadruplexes based on the d(TGGGAG) sequence. Our results demonstrate that the 5'-end conjugation does not necessarily increase the folding rate of the G-quadruplex; indeed, it ascribes anti-HIV activity. Unexpectedly, the G4-folding kinetics of the inactive G4 is similar to that of the 5'-end modified sequences. ESI-MS studies also revealed the formation of higher order G4 structures identified as octameric complexes along with tetramolecular G-quadruplexes.

Keywords: Anti-HIV aptamers; kinetic studies; mass spectrometry; modified oligonucleotides; tetramolecular G-quadruplexes.