3ZPU

Design and Synthesis of P1-P3 Macrocyclic Tertiary Alcohol Comprising HIV-1 Protease Inhibitors

3ZPU の概要

• エントリーDOI: 10.2210/pdb3zpu/pdb
• 関連するPDBエントリー: 3ZPS 3ZPT
• 分子名称: PROTEASE, CHLORIDE ION, methyl N-[(2S)-1-[2-[(4-bromophenyl)methyl]-2-[3-[(3Z,8S,11R)-8-tert-butyl-11-oxidanyl-7,10-bis(oxidanylidene)-6,9-diazabicyclo[11.2.2]heptadeca-1(15),3,13,16-tetraen-11-yl]propyl]hydrazinyl]-3,3-dimethyl-1-oxidanylidene-butan-2-yl]carbamate, ... (4 entities in total)
• 機能のキーワード: hydrolase, protease inhibitor, rational drug design
• 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 : P03366
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22400.42

構造登録者

Joshi, A.,Veron, J.B.,Unge, J.,Rosenquist, A.,Wallberg, H.,Samuelsson, B.,Hallberg, A.,Larhed, M. (登録日: 2013-03-01, 公開日: 2013-11-06, 最終更新日: 2024-05-01)

主引用文献

Joshi, A.,Veron, J.B.,Unge, J.,Rosenquist, A.,Wallberg, H.,Samuelsson, B.,Hallberg, A.,Larhed, M.
Design and Synthesis of P1-P3 Macrocyclic Tertiary Alcohol Comprising HIV-1 Protease Inhibitors
J.Med.Chem., 56:8999-, 2013

PubMed Abstract: To study P1-P3 macrocyclizations of previously reported tertiary-alcohol-comprising HIV-1 protease inhibitors (PIs), three new 14- and 15-member macrocyclic PIs were designed, synthesized by ring-closing metathesis, and evaluated alongside with 10 novel linear PIs. Cocrystallized complexes of the macrocyclic PIs and the HIV-1 protease are presented, analyzed, and discussed. The macrocyclic structures exhibited higher activities than the linear precursors with Ki and EC50 values down to 3.1 nM and 0.37 μM, respectively.

PubMed: 24160253
DOI: 10.1021/JM400811D

実験手法

X-RAY DIFFRACTION (1.8 Å)