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Crystal structures of HIV-1 reverse transcriptase with picomolar inhibitors reveal key interactions for drug design.

ABSTRACT: X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.

SUBMITTER: Frey KM

PROVIDER: S-EPMC3518392 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Crystal structures of HIV-1 reverse transcriptase with picomolar inhibitors reveal key interactions for drug design.

Frey Kathleen M KM Bollini Mariela M Mislak Andrea C AC Cisneros José A JA Gallardo-Macias Ricardo R Jorgensen William L WL Anderson Karen S KS

Journal of the American Chemical Society 20121119 48

X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles. ...[more]

PMID: 23163887

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Picomolar Inhibitors of HIV-1 Reverse Transcriptase: Design and Crystallography of Naphthyl Phenyl Ethers.

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Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability.

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| S-EPMC3847232 | biostudies-literature

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