8f0f | pdb_00008f0f

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

spinqualitylabelsall models 8f0f, resolution 1.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8f0f is a 2 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, GOL, NA, X7H Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5RZ08_9HIV1 Publication Abstract from PubMed 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. Evaluation of Darunavir-derived HIV-1 protease inhibitors incorporating P2' amide-derivatives: Synthesis, biological evaluation and structural studies.,Ghosh AK, Shahabi D, Kipfmiller M, Ghosh AK, Johnson M, Wang YF, Agniswamy J, Amano M, Weber IT, Mitsuya H Bioorg Med Chem Lett. 2023 Feb 2:129168. doi: 10.1016/j.bmcl.2023.129168. PMID:36738797 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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