1QBT

HIV-1 PROTEASE INHIBITORS WIIH LOW NANOMOLAR POTENCY

1QBT の概要

• エントリーDOI: 10.2210/pdb1qbt/pdb
• 分子名称: HIV-1 PROTEASE, [4R-(4ALPHA,5ALPHA,6ALPHA,7ALPHA)]-3,3'-{{TETRAHYDRO-5,6-DIHYDROXY-2-OXO-4,7-BIS(PHENYLMETHYL)-1H-1,3-DIAZEPINE-1,3(2H)-DIYL]BIS(METHYLENE)]BIS[N-1H-BENZIMIDAZOL-2-YLBENZAMIDE] (2 entities in total)
• 機能のキーワード: hydrolase (acid proteinase), aspartyl protease
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22340.25

構造登録者

Ala, P.,Chang, C.-H. (登録日: 1997-04-25, 公開日: 1997-10-15, 最終更新日: 2024-02-14)

主引用文献

Jadhav, P.K.,Ala, P.,Woerner, F.J.,Chang, C.H.,Garber, S.S.,Anton, E.D.,Bacheler, L.T.
Cyclic urea amides: HIV-1 protease inhibitors with low nanomolar potency against both wild type and protease inhibitor resistant mutants of HIV.
J.Med.Chem., 40:181-191, 1997

PubMed Abstract: Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have increased activity against drug-resistant mutants of the HIV PR. The design strategy for these inhibitors is based on the hypotheses that (i) the hydrogen-bonding interactions between the inhibitor and the protease backbone will remain constant for wild-type and mutant enzymes and (ii) inhibitors which are capable of forming many nonbonded interactions, distributed throughout the active site, will experience a lower percent change in binding energy as a result of mutation in the target enzyme than those that form fewer interactions by partial occupation of the active site. The cyclic urea amide, SD146, forms 14 hydrogen bonds and 191 van der Waals contacts to HIV PR. SD146 is a very potent antiviral agent (IC90 = 5.1 nM) against wild-type HIV and maintains the same or improved level of high potency against a range of mutant strains of HIV with resistance to a wide variety of HIV protease inhibitors.

PubMed: 9003516
DOI: 10.1021/jm960586t

実験手法

X-RAY DIFFRACTION (2.1 Å)