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| - | [[Image:1jlq.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1jlq| PDB=1jlq | SCENE= }} | | {{STRUCTURE_1jlq| PDB=1jlq | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH 739W94'''
| + | ===CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH 739W94=== |
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| - | ==Overview==
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| - | A series of 2-amino-5-arylthiobenzonitriles (1) was found to be active against HIV-1. Structural modifications led to the sulfoxides (2) and sulfones (3). The sulfoxides generally showed antiviral activity against HIV-1 similar to that of 1. The sulfones, however, were the most potent series of analogues, a number having activity against HIV-1 in the nanomolar range. Structural-activity relationship (SAR) studies suggested that a meta substituent, particularly a meta methyl substituent, invariably increased antiviral activities. However, optimal antiviral activities were manifested by compounds where both meta groups in the arylsulfonyl moiety were substituted and one of the substituents was a methyl group. Such a disubstitution led to compounds 3v, 3w, 3x, and 3y having IC50 values against HIV-1 in the low nanomolar range. When gauged for their broad-spectrum antiviral activity against key non-nucleoside reverse transcriptase inhibitor (NNRTI) related mutants, all the di-meta-substituted sulfones 3u-z and the 2-naphthyl analogue 3ee generally showed single-digit nanomolar activity against the V106A and P236L strains and submicromolar to low nanomolar activity against strains E138K, V108I, and Y188C. However, they showed a lack of activity against the K103N and Y181C mutant viruses. The elucidation of the X-ray crystal structure of the complex of 3v (739W94) in HIV-1 reverse transcriptase showed an overlap in the binding domain when compared with the complex of nevirapine in HIV-1 reverse transcriptase. The X-ray structure allowed for the rationalization of SAR data and potencies of the compounds against the mutants.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11384233}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11384233 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11384233}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Hiv-1 reverse transcriptase]] | | [[Category: Hiv-1 reverse transcriptase]] |
| | [[Category: Non-nucleoside inhibitor]] | | [[Category: Non-nucleoside inhibitor]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:22:44 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 20:26:28 2008'' |
Revision as of 17:26, 1 July 2008
Template:STRUCTURE 1jlq
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH 739W94
Template:ABSTRACT PUBMED 11384233
About this Structure
1JLQ is a Protein complex structure of sequences from Human immunodeficiency virus type 1 (isolate hxb2). Full crystallographic information is available from OCA.
Reference
2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1., Chan JH, Hong JS, Hunter RN 3rd, Orr GF, Cowan JR, Sherman DB, Sparks SM, Reitter BE, Andrews CW 3rd, Hazen RJ, St Clair M, Boone LR, Ferris RG, Creech KL, Roberts GB, Short SA, Weaver K, Ott RJ, Ren J, Hopkins A, Stuart DI, Stammers DK, J Med Chem. 2001 Jun 7;44(12):1866-82. PMID:11384233
Page seeded by OCA on Tue Jul 1 20:26:28 2008
