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Sci. Pharm. 2015, 83(3), 535-548; doi:10.3797/scipharm.1502-01

Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase-1-Targeting Compound

1
Center for Sickle Cell Disease, Howard University, Washington DC 20059, USA
2
Department of Pharmacology, Howard University, Washington DC 20059, USA
3
Department of Pharmaceutical Sciences, Howard University, Washington DC 20059, USA
4
College of Engineering, Howard University, Washington DC 20059, USA
5
Department of Biochemistry, School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio TX 78229, USA
6
Enamine LLC, Princeton Corporate Plaza, 7 Deer Park Drive, Ste. M-3 Monmouth Jct., NJ 08852, USA
7
Department of Microbiology, College of Medicine, Howard University, Washington DC 20059, USA
8
Department of Medicine, Howard University, Washington DC 20059, USA
*
Author to whom correspondence should be addressed.
Received: 4 February 2015 / Accepted: 22 June 2015 / Published: 22 June 2015
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Abstract

Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that targeted PP1 and identified a compound, SMAPP1, which induced HIV-1 transcription. However, this compound has a limited bioavailability in vivo and may not be able to reach HIV-1-infected cells and induce HIV-1 transcription in patients. We packaged SMAPP1 in polymeric polyethylene glycol polymethyl methacrylate nanoparticles and analyzed its release and the effect on HIV-1 transcription in a cell culture. SMAPP1 was efficiently packaged in the nanoparticles and released during a 120-hr period. Treatment of the HIV-1-infected cells with the SMAPP1-loaded nanoparticles induced HIV-1 transcription. Thus, nanoparticles loaded with HIV-1-targeting compounds might be useful for future anti-HIV-1 therapeutics.
Keywords: HIV-1; Transcription; Latency; Nanoparticles; Small molecules; PP1; SMAPP1 HIV-1; Transcription; Latency; Nanoparticles; Small molecules; PP1; SMAPP1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

SMITH, K.A.; LIN, X.; BOLSHAKOV, O.; GRIFFIN, J.; NIU, X.; KOVALSKYY, D.; IVANOV, A.; JEREBTSOVA, M.; TAYLOR, R.E.; AKALA, E.; NEKHAI, S. Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase-1-Targeting Compound. Sci. Pharm. 2015, 83, 535-548.

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