Inhibitory effects of archetypical nucleic acid ligands on the interactions of HIV-1 nucleocapsid protein with elements of Psi-RNA

Nucleic Acids Research
Kevin B TurnerDaniele Fabris

Abstract

Disrupting the interactions between human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) protein and structural elements of the packaging signal (Psi-RNA) could constitute an ideal strategy to inhibit the functions of this region of the genome leader in the virus life cycle. We have employed electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS) to assess the ability of a series of nucleic acid ligands to bind selected structures of Psi-RNA and inhibit their specific interactions with NC in vitro. We found that the majority of the ligands included in the study were able to form stable non-covalent complexes with stem-loop 2, 3 and 4 (SL2-4), consistent with their characteristic nucleic acid binding modes. However, only aminoglycosidic antibiotics were capable of dissociating preformed NC*SL3 and NC*SL4 complexes, but not NC*SL2. The apparent specificity of these inhibitory effects is closely dependent on distinctive structural features of the different NC*RNA complexes. The trends observed for the IC50 values correlate very well with those provided by the ligand binding affinities and the dissociation constants of target NC*RNA complexes. This systematic investigation of archetypical nucleic acid liga...Continue Reading

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Citations

Jul 29, 2006·Journal of the American Society for Mass Spectrometry·Kevin B TurnerDaniele Fabris
Nov 10, 2009·Journal of the American Society for Mass Spectrometry·Daniele Fabris
Jun 10, 2011·Analytical Chemistry·D Fabris
Apr 7, 2012·Journal of Medicinal Chemistry·Douglas M Warui, Anne M Baranger
Aug 19, 2011·AIDS Research and Human Retroviruses·Abdul A Waheed, Eric O Freed
Apr 11, 2008·Nucleic Acids Research·Kevin B TurnerDaniele Fabris
Sep 6, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sarah E EvansVeronika A Szalai
Feb 13, 2016·Rapid Communications in Mass Spectrometry : RCM·Jennifer L LippensD Fabris
Sep 29, 2009·Antiviral Research·Catherine S Adamson, Eric O Freed
May 31, 2015·Biotechnology Advances·Kirk K HouSamuel A Wickline
Jun 8, 2014·Virus Research·Jean-Luc DarlixYves Mély
May 1, 2007·Journal of Molecular Biology·Kevin B TurnerDaniele Fabris
Jul 16, 2014·Virus Research·Divita Garg, Bruce E Torbett
Mar 23, 2013·Journal of the American Chemical Society·William StephensonPan T X Li
Mar 17, 2012·Journal of the American Chemical Society·Annalisa ArcellaModesto Orozco
Nov 20, 2016·Chemical Communications : Chem Comm·Sarah R SpellNicholas P Farrell
Oct 1, 2021·Chemical Reviews·Eric LargyValérie Gabelica

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Methods Mentioned

BETA
footprinting

Software Mentioned

Origin
SL3
XMASS

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