Publications by authors named "Peter J Slavish"
Article Synopsis
- Influenza remains a major cause of death globally, leading to efforts to develop antiviral strategies that have been met with resistance from the virus, including resistance to the new drug baloxavir marboxil.
- Researchers have leveraged structural insights from endonuclease-substrate complexes to design new inhibitor molecules that specifically target the endonuclease, aiming to minimize the chances of resistance mutations.
- The team successfully created potent inhibitors effective against both normal and resistant strains of the endonuclease, including macrocyclic versions, and also identified ways to enhance the effectiveness of these cyclic compounds based on structural analysis.
The Bromodomain and Extra-Terminal domain (BET) family of proteins are involved in the regulation of gene transcription, and their dysregulation is implicated in several diseases including cancer. BET proteins contain two tandem bromodomains (BD1 and BD2) that independently recognize acetylated-lysine residues and appear to have distinct biological roles. We compared several published co-crystal structures and found five positions near the substrate binding pocket that vary between BET bromodomains.
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- - The BET protein family, including isoforms BRD2, BRD3, BRD4, and BRDT, is being investigated as a potential target for drugs related to cancer, autoimmune diseases, heart issues, and male contraception, due to their unique bromodomains that interact with acetylated-lysine residues.
- - Researchers designed a new series of tetrahydroquinolines (THQ) aimed at selectively targeting these bromodomains by manipulating water interactions in the binding pocket, with one compound, SJ830599 (9), showing promising selectivity for the BRD2-BD2 isoform.
- - Binding studies revealed that SJ830599's interaction with BRD2-BD2 is heavily