1HVR

RATIONAL DESIGN OF POTENT, BIOAVAILABLE, NONPEPTIDE CYCLIC UREAS AS HIV PROTEASE INHIBITORS

1HVR の概要

• エントリーDOI: 10.2210/pdb1hvr/pdb
• 分子名称: HIV-1 PROTEASE, [4R-(4ALPHA,5ALPHA,6BETA,7BETA)]-HEXAHYDRO-5,6-DIHYDROXY-1,3-BIS[2-NAPHTHYL-METHYL]-4,7-BIS(PHENYLMETHYL)-2H-1,3-DIAZEPIN-2-ONE (2 entities in total)
• 機能のキーワード: hydrolase, acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 22154.08

構造登録者

Chang, C.-H. (登録日: 1994-02-14, 公開日: 1995-01-26, 最終更新日: 2024-10-16)

主引用文献

Lam, P.Y.,Jadhav, P.K.,Eyermann, C.J.,Hodge, C.N.,Ru, Y.,Bacheler, L.T.,Meek, J.L.,Otto, M.J.,Rayner, M.M.,Wong, Y.N.,Chang, C.-H.,Weber, P.,Jackson, D.A.,Sharpe, T.R.,Erickson-Viitanen, S.
Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors.
Science, 263:380-384, 1994

PubMed Abstract: Mechanistic information and structure-based design methods have been used to design a series of nonpeptide cyclic ureas that are potent inhibitors of human immunodeficiency virus (HIV) protease and HIV replication. A fundamental feature of these inhibitors is the cyclic urea carbonyl oxygen that mimics the hydrogen-bonding features of a key structural water molecule. The success of the design in both displacing and mimicking the structural water molecule was confirmed by x-ray crystallographic studies. Highly selective, preorganized inhibitors with relatively low molecular weight and high oral bioavailability were synthesized.

PubMed: 8278812

実験手法

X-RAY DIFFRACTION (1.8 Å)