6DV0

HIV-1 wild type protease with GRL-02815A, a thiochroman heterocycle with (S)-Boc-amine functionality as the P2 ligand

Summary for 6DV0

• Entry DOI: 10.2210/pdb6dv0/pdb
• Related: 2IEN 6DV4
• Descriptor: Protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: aspartic acid protease, hiv-1 protease inhibitor of grl-02815a, thiochroman, p2 ligand, drug resistance, design and synthesis, hydrolase, antiviral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 2
• Total formula weight: 22365.25

Authors

Wang, Y.-F.,Agniswamy, J.,Weber, I.T. (deposition date: 2018-06-22, release date: 2018-10-31, Last modification date: 2023-10-11)

Primary citation

Ghosh, A.K.,Jadhav, R.D.,Simpson, H.,Kovela, S.,Osswald, H.,Agniswamy, J.,Wang, Y.F.,Hattori, S.I.,Weber, I.T.,Mitsuya, H.
Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands.
Eur J Med Chem, 160:171-182, 2018

PubMed Abstract: We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.

PubMed: 30340140
DOI: 10.1016/j.ejmech.2018.09.046

Experimental method

X-RAY DIFFRACTION (1.2 Å)