Literature DB >> 23163887

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

Kathleen M Frey1, Mariela Bollini, Andrea C Mislak, José A Cisneros, Ricardo Gallardo-Macias, William L Jorgensen, Karen S Anderson.   

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.

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Year:  2012        PMID： 23163887      PMCID： PMC3518392          DOI： 10.1021/ja3092642

Source DB:  PubMed          Journal:  J Am Chem Soc        ISSN： 0002-7863            Impact factor:   15.419


  18 in total

1.  Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses.

Authors:  Denis J Kertesz; Christine Brotherton-Pleiss; Minmin Yang; Zhanguo Wang; Xianfeng Lin; Zongxing Qiu; Donald R Hirschfeld; Shelley Gleason; Taraneh Mirzadegan; Pete W Dunten; Seth F Harris; Armando G Villaseñor; Julie Qi Hang; Gabrielle M Heilek; Klaus Klumpp
Journal:  Bioorg Med Chem Lett       Date:  2010-05-16       Impact factor: 2.823

2.  Probing nonnucleoside inhibitor-induced active-site distortion in HIV-1 reverse transcriptase by transient kinetic analyses.

Authors:  Qing Xia; Jessica Radzio; Karen S Anderson; Nicolas Sluis-Cremer
Journal:  Protein Sci       Date:  2007-08       Impact factor: 6.725

3.  Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains.

Authors:  Daniel M Himmel; Kalyan Das; Arthur D Clark; Stephen H Hughes; Abdellah Benjahad; Said Oumouch; Jérôme Guillemont; Sophie Coupa; Alain Poncelet; Imre Csoka; Christophe Meyer; Koen Andries; Chi Hung Nguyen; David S Grierson; Eddy Arnold
Journal:  J Med Chem       Date:  2005-12-01       Impact factor: 7.446

4.  Structural basis of asymmetry in the human immunodeficiency virus type 1 reverse transcriptase heterodimer.

Authors:  J Wang; S J Smerdon; J Jäger; L A Kohlstaedt; P A Rice; J M Friedman; T A Steitz
Journal:  Proc Natl Acad Sci U S A       Date:  1994-07-19       Impact factor: 11.205

5.  Mutational analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors.

Authors:  H Pelemans; R Esnouf; E De Clercq; J Balzarini
Journal:  Mol Pharmacol       Date:  2000-05       Impact factor: 4.436

6.  The N137 and P140 amino acids in the p51 and the P95 amino acid in the p66 subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are instrumental to maintain catalytic activity and to design new classes of anti-HIV-1 drugs.

Authors:  Joeri Auwerx; Joke Van Nieuwenhove; Fátima Rodríguez-Barrios; Sonia de Castro; Sonsoles Velázquez; Francesca Ceccherini-Silberstein; Erik De Clercq; María-José Camarasa; Carlo-Federico Perno; Federico Gago; Jan Balzarini
Journal:  FEBS Lett       Date:  2005-04-25       Impact factor: 4.124

7.  High sequence conservation of human immunodeficiency virus type 1 reverse transcriptase under drug pressure despite the continuous appearance of mutations.

Authors:  Francesca Ceccherini-Silberstein; Federico Gago; Maria Santoro; Caterina Gori; Valentina Svicher; Fátima Rodríguez-Barrios; Roberta d'Arrigo; Massimo Ciccozzi; Ada Bertoli; Antonella d'Arminio Monforte; Jan Balzarini; Andrea Antinori; Carlo-Federico Perno
Journal:  J Virol       Date:  2005-08       Impact factor: 5.103

8.  Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants.

Authors:  Kalyan Das; Arthur D Clark; Paul J Lewi; Jan Heeres; Marc R De Jonge; Lucien M H Koymans; H Maarten Vinkers; Frederik Daeyaert; Donald W Ludovici; Michael J Kukla; Bart De Corte; Robert W Kavash; Chih Y Ho; Hong Ye; Mark A Lichtenstein; Koen Andries; Rudi Pauwels; Marie-Pierre De Béthune; Paul L Boyer; Patrick Clark; Stephen H Hughes; Paul A J Janssen; Eddy Arnold
Journal:  J Med Chem       Date:  2004-05-06       Impact factor: 7.446

9.  High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations.

Authors:  Kalyan Das; Joseph D Bauman; Arthur D Clark; Yulia V Frenkel; Paul J Lewi; Aaron J Shatkin; Stephen H Hughes; Eddy Arnold
Journal:  Proc Natl Acad Sci U S A       Date:  2008-01-29       Impact factor: 11.205

10.  Phaser crystallographic software.

Authors:  Airlie J McCoy; Ralf W Grosse-Kunstleve; Paul D Adams; Martyn D Winn; Laurent C Storoni; Randy J Read
Journal:  J Appl Crystallogr       Date:  2007-07-13       Impact factor: 3.304
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  21 in total

1.  Double Variational Binding--(SMILES) Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands.

Authors:  Mihai V Putz; Nicoleta A Dudaș; Adriana Isvoran
Journal:  Int J Mol Sci       Date:  2015-08-18       Impact factor: 5.923

2.  Pharmacophore-based screening and drug repurposing exemplified on glycogen synthase kinase-3 inhibitors.

Authors:  Luminita Crisan; Sorin Avram; Liliana Pacureanu
Journal:  Mol Divers       Date:  2017-01-21       Impact factor: 2.943

3.  Predicting Binding Free Energies in a Large Combinatorial Chemical Space Using Multisite λ Dynamics.

Authors:  Jonah Z Vilseck; Kira A Armacost; Ryan L Hayes; Garrett B Goh; Charles L Brooks
Journal:  J Phys Chem Lett       Date:  2018-06-06       Impact factor: 6.475

4.  Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance.

Authors:  William T Gray; Kathleen M Frey; Sarah B Laskey; Andrea C Mislak; Krasimir A Spasov; Won-Gil Lee; Mariela Bollini; Robert F Siliciano; William L Jorgensen; Karen S Anderson
Journal:  ACS Med Chem Lett       Date:  2015-08-31       Impact factor: 4.345

5.  Computer-aided discovery of anti-HIV agents.

Authors:  William L Jorgensen
Journal:  Bioorg Med Chem       Date:  2016-07-21       Impact factor: 3.641

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

Authors:  Won-Gil Lee; Kathleen M Frey; Ricardo Gallardo-Macias; Krasimir A Spasov; Mariela Bollini; Karen S Anderson; William L Jorgensen
Journal:  ACS Med Chem Lett       Date:  2014-10-13       Impact factor: 4.345

Review 7.  Evolving understanding of HIV-1 reverse transcriptase structure, function, inhibition, and resistance.

Authors:  Francesc Xavier Ruiz; Eddy Arnold
Journal:  Curr Opin Struct Biol       Date:  2020-01-11       Impact factor: 6.809

8.  Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase.

Authors:  Tomoaki Sasaki; Zachary T K Gannam; Shalley N Kudalkar; Kathleen M Frey; Won-Gil Lee; Krasimir A Spasov; William L Jorgensen; Karen S Anderson
Journal:  Bioorg Med Chem Lett       Date:  2019-06-26       Impact factor: 2.823

9.  Structural and pharmacological evaluation of a novel non-nucleoside reverse transcriptase inhibitor as a promising long acting nanoformulation for treating HIV.

Authors:  Shalley N Kudalkar; Irfan Ullah; Nicole Bertoletti; Hanna K Mandl; José A Cisneros; Jagadish Beloor; Albert H Chan; Elias Quijano; W Mark Saltzman; William L Jorgensen; Priti Kumar; Karen S Anderson
Journal:  Antiviral Res       Date:  2019-04-26       Impact factor: 5.970

10.  Structure-based evaluation of C5 derivatives in the catechol diether series targeting HIV-1 reverse transcriptase.

Authors:  Kathleen M Frey; William T Gray; Krasimir A Spasov; Mariela Bollini; Ricardo Gallardo-Macias; William L Jorgensen; Karen S Anderson
Journal:  Chem Biol Drug Des       Date:  2014-03-14       Impact factor: 2.817
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