8F0F

HIV-1 wild type protease with GRL-110-19A, a chloroacetamide derivative based on Darunavir as P2' group

8F0F の概要

• エントリーDOI: 10.2210/pdb8f0f/pdb
• 関連するPDBエントリー: 2IEN 6U7O
• 分子名称: Protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: aspartic acid protease, hiv-1 protease, darunavir, a chloroacetamide derivative inhibitor, antiviral protein, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22326.94

構造登録者

Wang, Y.-F.,Agniswamy, J.,Ghosh, A.K.,Weber, I.T. (登録日: 2022-11-02, 公開日: 2023-02-15, 最終更新日: 2023-10-25)

主引用文献

Ghosh, A.K.,Shahabi, D.,Kipfmiller, M.,Ghosh, A.K.,Johnson, M.,Wang, Y.F.,Agniswamy, J.,Amano, M.,Weber, I.T.,Mitsuya, H.
Evaluation of darunavir-derived HIV-1 protease inhibitors incorporating P2' amide-derivatives: Synthesis, biological evaluation and structural studies.
Bioorg.Med.Chem.Lett., 83:129168-129168, 2023

PubMed Abstract: We report here the synthesis and biological evaluation of darunavir derived HIV-1 protease inhibitors and their functional effect on enzyme inhibition and antiviral activity in MT-2 cell lines. The P2' 4-amino functionality was modified to make a number of amide derivatives to interact with residues in the S2' subsite of the HIV-1 protease active site. Several compounds exhibited picomolar enzyme inhibitory and low nanomolar antiviral activity. The X-ray crystal structure of the chloroacetate derivative bound to HIV-1 protease was determined. Interestingly, the active chloroacetate group converted to the acetate functionality during X-ray exposure. The structure revealed that the P2' carboxamide functionality makes enhanced hydrogen bonding interactions with the backbone atoms in the S2'-subsite.

PubMed: 36738797
DOI: 10.1016/j.bmcl.2023.129168

実験手法

X-RAY DIFFRACTION (1.29 Å)