Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghosh AK, Shahabi D, Kipfmiller M, Ghosh AK, Johnson M, Wang YF, Agniswamy J, Amano M, Weber IT, Mitsuya H. Evaluation of darunavir-derived HIV-1 protease inhibitors incorporating P2' amide-derivatives: Synthesis, biological evaluation and structural studies. Bioorg Med Chem Lett. 2023 Mar 1;83:129168. PMID:36738797 doi:10.1016/j.bmcl.2023.129168
