Synthesis of distal and proximal fleximer base analogues and evaluation in the nucleocapsid protein of HIV-1 |
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| Affiliation: | 1. University of Maryland, Baltimore County, Department of Chemistry and Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA;2. University of Siena, Department of Biotechnology, Chemistry and Pharmacy, via Aldo Moro 2, 53100 Siena, Italy;3. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Bldg., Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA;4. Howard Hughes Medical Institute, USA |
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| Abstract: | Anti-HIV-1 drug design has been notably challenging due to the virus’ ability to mutate and develop immunity against commercially available drugs. The aims of this project were to develop a series of fleximer base analogues that not only possess inherent flexibility that can remain active when faced with binding site mutations, but also target a non-canonical, highly conserved target: the nucleocapsid protein of HIV (NC). The compounds were predicted by computational studies not to function via zinc ejection, which would endow them with significant advantages over non-specific and thus toxic zinc-ejectors. The target fleximer bases were synthesized using palladium-catalyzed cross-coupling techniques and subsequently tested against NC and HIV-1. The results of those studies are described herein. |
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| Keywords: | Fleximers Pyrimidine HIV-1 NC Synthesis |
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