556107-64-3Relevant articles and documents
Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead
Ippolito, Joseph A.,Niu, Haichan,Bertoletti, Nicole,Carter, Zachary J.,Jin, Shengyan,Spasov, Krasimir A.,Cisneros, José A.,Valhondo, Margarita,Cutrona, Kara J.,Anderson, Karen S.,Jorgensen, William L.
supporting information, p. 249 - 255 (2021/01/26)
Covalent inhibitors of wild-type HIV-1 reverse transcriptase (CRTIs) are reported. Three compounds derived from catechol diether non-nucleoside inhibitors (NNRTIs) with addition of a fluorosulfate warhead are demonstrated to covalently modify Tyr181 of HIV-RT. X-ray crystal structures for complexes of the CRTIs with the enzyme are provided, which fully demonstrate the covalent attachment, and confirmation is provided by appropriate mass shifts in ESI-TOF mass spectra. The three CRTIs and six noncovalent analogues are found to be potent inhibitors with both IC50 values for in vitro inhibition of WT RT and EC50 values for cytopathic protection of HIV-1-infected human T-cells in the 5-320 nM range.
Picomolar inhibitors of HIV-1 reverse transcriptase: Design and crystallography of naphthyl phenyl ethers
Lee, Won-Gil,Frey, Kathleen M.,Gallardo-Macias, Ricardo,Spasov, Krasimir A.,Bollini, Mariela,Anderson, Karen S.,Jorgensen, William L.
supporting information, p. 1259 - 1262 (2015/04/27)
Catechol diethers that incorporate a 6-cyano-1-naphthyl substituent have been explored as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Promising compounds are reported that show midpicomolar activity against the wild-type virus and sub-20 nM activity against viral variants bearing Tyr181Cys and Lys103Asn mutations in HIV-RT. An X-ray crystal structure at 2.49 ? resolution is also reported for the key compound 6e with HIV-RT.
