5DGU

Crystal Structure of HIV-1 Protease Inhibitors Containing Substituted fused-Tetrahydropyranyl Tetrahydrofuran as P2-Ligand GRL-004-11A

Summary for 5DGU

• Entry DOI: 10.2210/pdb5dgu/pdb
• Descriptor: Pol protein, (3R,3aR,4S,7aS)-3-methoxyhexahydro-4H-furo[2,3-b]pyran-4-yl [(2S,3R)-3-hydroxy-4-{[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino}-1-phenylbutan-2-yl]carbamate, SODIUM ION, ... (6 entities in total)
• Functional Keywords: hiv-1 protease, enzyme, hydrolase, hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 2
• Total formula weight: 22299.46

Authors

Agniswamy, J.,Wang, Y.-F.,Weber, I.T. (deposition date: 2015-08-28, release date: 2015-10-28, Last modification date: 2023-09-27)

Primary citation

Ghosh, A.K.,Martyr, C.D.,Kassekert, L.A.,Nyalapatla, P.R.,Steffey, M.,Agniswamy, J.,Wang, Y.F.,Weber, I.T.,Amano, M.,Mitsuya, H.
Design, synthesis, biological evaluation and X-ray structural studies of HIV-1 protease inhibitors containing substituted fused-tetrahydropyranyl tetrahydrofuran as P2-ligands.
Org.Biomol.Chem., 13:11607-11621, 2015

PubMed Abstract: Design, synthesis, biological and X-ray crystallographic studies of a series of potent HIV-1 protease inhibitors are described. Various polar functionalities have been incorporated on the tetrahydropyranyl-tetrahydrofuran-derived P2 ligand to interact with the backbone atoms in the S2-subsite. The majority of the inhibitors showed very potent enzyme inhibitory and antiviral activity. Two high-resolution X-ray structures of 30b- and 30j-bound HIV-1 protease provide insight into ligand-binding site interactions. In particular, the polar functionalities on the P2-ligand appear to form unique hydrogen bonds with Gly48 amide NH and amide carbonyl groups in the flap region.

PubMed: 26462551
DOI: 10.1039/c5ob01930c

Experimental method

X-RAY DIFFRACTION (1.22 Å)