5AH9

Disubstituted bis-THF moieties as new P2 ligands in non-peptidal HIV- 1 Protease Inhibitors (II)

5AH9 の概要

• エントリーDOI: 10.2210/pdb5ah9/pdb
• 関連するPDBエントリー: 5AGZ 5AH6 5AH7 5AH8 5AHA 5AHB 5AHC
• 分子名称: PROTEASE, CHLORIDE ION, (3R,3aS,4R,6aR)-4-(2-methoxyethoxy)hexahydrofuro[2,3-b]furan-3-yl [(2S,3R)-4-{[(4-aminophenyl)sulfonyl](2-methylpropyl)amino}-3-hydroxy-1-phenylbutan-2-yl]carbamate, ... (4 entities in total)
• 機能のキーワード: hydrolase, inhibitor, rational drug design, bis-thf bis-diol
• 由来する生物種: HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (Z2/CDC-Z34 ISOLATE)
• 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 : P03366
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22279.42

構造登録者

Hohlfeld, K.,Wegner, J.K.,Kesteleyn, B.,Linclau, B.,Enstrom, O.,Unge, J. (登録日: 2015-02-05, 公開日: 2015-05-06, 最終更新日: 2024-05-01)

主引用文献

Hohlfeld, K.,Wegner, J.,Kesteleyn, B.,Linclau, B.,Unge, J.
Disubstituted Bis-Thf Moieties as New P2 Ligands in Non-Peptidal HIV-1 Protease Inhibitors (II).
J.Med.Chem., 58:4029-, 2015

PubMed Abstract: A series of darunavir analogues featuring a substituted bis-THF ring as P2 ligand have been synthesized and evaluated. Very high affinity protease inhibitors (PIs) with an interesting activity on wild-type HIV and a panel of multi-PI resistant HIV-1 mutants containing clinically observed, primary mutations were identified using a cell-based assay. Crystal structure analysis was conducted on a number of PI analogues in complex with HIV-1 protease.

PubMed: 25897791
DOI: 10.1021/ACS.JMEDCHEM.5B00358

実験手法

X-RAY DIFFRACTION (1.44 Å)