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

Kathleen M. Frey; Mariela Bollini; Andrea C. Mislak; José A. Cisneros; Ricardo Gallardo-Macias; William L. Jorgensen; Karen S. Anderson

doi:10.1021/ja3092642

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

Kathleen M. Frey
, Mariela Bollini
, Andrea C. Mislak
, José A. Cisneros
, Ricardo Gallardo-Macias
, William L. Jorgensen
, Karen S. Anderson

Institute for Therapeutics Discovery and Development

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

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.

Original language	English (US)
Pages (from-to)	19501-19503
Number of pages	3
Journal	Journal of the American Chemical Society
Volume	134
Issue number	48
DOIs	https://doi.org/10.1021/ja3092642
State	Published - Dec 5 2012

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10.1021/ja3092642

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abstract = "X-ray crystal structures at 2.9 {\AA} 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.",

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AU - Frey, Kathleen M.

AU - Bollini, Mariela

AU - Mislak, Andrea C.

AU - Cisneros, José A.

AU - Gallardo-Macias, Ricardo

AU - Jorgensen, William L.

AU - Anderson, Karen S.

PY - 2012/12/5

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AB - 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.

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JF - Journal of the American Chemical Society

IS - 48

ER -

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

Abstract

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