7U5Z

Crystal Structure of HIV-1 Reverse Transcriptase in Complex with JLJ353

Summary for 7U5Z

• Entry DOI: 10.2210/pdb7u5z/pdb
• Descriptor: Reverse transcriptase/ribonuclease H, p51 RT, 2-chloro-4-({5-[(2,6-difluorophenyl)methyl]-1,3-oxazol-2-yl}amino)benzonitrile, ... (4 entities in total)
• Functional Keywords: reverse transcriptase, antiviral, drug design, viral protein, hiv-1
• Biological source: Human immunodeficiency virus type 1 BH10; More
• Total number of polymer chains: 2
• Total formula weight: 114374.46

Authors

Hollander, K.,Carter, Z.,Jorgensen, W.L.,Anderson, K.S. (deposition date: 2022-03-03, release date: 2023-03-15, Last modification date: 2023-10-25)

Primary citation

Carter, Z.J.,Hollander, K.,Spasov, K.A.,Anderson, K.S.,Jorgensen, W.L.
Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase.
Bioorg.Med.Chem.Lett., 84:129216-129216, 2023

PubMed Abstract: We report non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) using a biphenylmethyloxazole pharmacophore. A crystal structure of benzyloxazole 1 was obtained and suggested the potential viability of biphenyl analogues. In particular, 6a, 6b, and 7 turned out to be potent NNRTIs with low-nanomolar activity in enzyme inhibition and infected T-cell assays, and with low cytotoxicity. Though modeling further suggested that analogues with fluorosulfate and epoxide warheads might provide covalent modification of Tyr188, synthesis and testing did not find evidence for this outcome.

PubMed: 36871704
DOI: 10.1016/j.bmcl.2023.129216

Experimental method

X-RAY DIFFRACTION (2.3 Å)