9B2H

HIV-1 wild type protease with GRL-072-17A, a substituted tetrahydrofuran derivative based on Darunavir as P2 group

This is a non-PDB format compatible entry.

Summary for 9B2H

• Entry DOI: 10.2210/pdb9b2h/pdb
• Related: 2IEN 3NU3
• Descriptor: Protease, SODIUM ION, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: aspartic acid protease, hiv-1 protease, darunavir, a substituted tetrahydrofuran derivative inhibitor, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 2
• Total formula weight: 22504.11

Authors

Wang, Y.-F.,Agniswamy, J.,Ghosh, A.K.,Weber, I.T. (deposition date: 2024-03-15, release date: 2024-07-24, Last modification date: 2024-10-02)

Primary citation

Ghosh, A.K.,Lee, D.,Sharma, A.,Johnson, M.E.,Ghosh, A.K.,Wang, Y.F.,Agniswamy, J.,Amano, M.,Hattori, S.I.,Weber, I.T.,Mitsuya, H.
Design of substituted tetrahydrofuran derivatives for HIV-1 protease inhibitors: synthesis, biological evaluation, and X-ray structural studies.
Org.Biomol.Chem., 22:7354-7372, 2024

PubMed Abstract: Substituted tetrahydrofuran derivatives were designed and synthesized to serve as the P2 ligand for a series of potent HIV-1 protease inhibitors. Both enantiomers of the tetrahydrofuran derivatives were synthesized stereoselectivity in optically active forms using lipase-PS catalyzed enzymatic resolution as the key step. These tetrahydrofuran derivatives are designed to promote hydrogen bonding and van der Waals interactions with the backbone atoms in the S2 subsite of the HIV-1 protease active site. Several inhibitors displayed very potent HIV-1 protease inhibitory activity. A high-resolution X-ray crystal structure of an inhibitor-bound HIV-1 protease provided important insight into the ligand binding site interactions in the active site.

PubMed: 38973505
DOI: 10.1039/d4ob00506f

Experimental method

X-RAY DIFFRACTION (1.32 Å)