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• W2022074021 abstract "The polymerase activity of HIV-1 reverse transcriptase (RT) is entirely dependent on the heterodimeric structure of the enzyme. Accordingly, RT dimerization represents a target for the development of a new therapeutic class of HIV inhibitors. We previously demonstrated that the N-3-ethyl derivative of 2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5' '-(4' '-amino-1' ',2' '-oxathiole-2' ',2' '-dioxide)thymine (TSAO-T) destabilizes the inter-subunit interactions of HIV-1 RT [Sluis-Cremer, N.; Dmietrinko, G. I.; Balzarini, J.; Camarasa, M.-J.; Parniak, M. A. Biochemistry 2000, 39, 1427-1433]. In the current study, we evaluated the ability of 64 TSAO-T derivatives to inhibit RT dimerization using a novel screening assay. Five derivatives were identified with improved activity compared to TSAO-T. Four of these harbored hydrophilic or aromatic substituents at the N3 position. Furthermore, a good correlation between the ability of the TSAO-T derivatives to inhibit RT dimerization and the enzyme's polymerase activity was also observed. This study provides an important framework for the rational design of more potent inhibitors of RT dimerization." @default.
• W2022074021 created "2016-06-24" @default.
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• W2022074021 date "2006-07-14" @default.
• W2022074021 modified "2023-10-17" @default.
• W2022074021 title "Structure−Activity Relationships of [2‘,5‘-Bis-<i>O</i>-(<i>tert</i>-butyldimethylsilyl)-β-<scp>d</scp>-ribofuranosyl]- 3‘-spiro-5‘ ‘-(4‘ ‘-amino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide)thymine Derivatives as Inhibitors of HIV-1 Reverse Transcriptase Dimerization" @default.
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• W2022074021 doi "https://doi.org/10.1021/jm0604575" @default.
• W2022074021 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16884295" @default.
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