9doj
Influenza A virus polymerase PA subunit endonuclease domain bound to inhibitor Compound 19aInfluenza A virus polymerase PA subunit endonuclease domain bound to inhibitor Compound 19a
Structural highlights
FunctionA0A075EM28_9INFA Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.[HAMAP-Rule:MF_04063] Publication Abstract from PubMedA novel, highly diastereoselective, and metal-free synthesis of multisubstituted piperidines via an S(N)1 approach is reported in this study. The method allows for the preparation of highly functionalized compounds with exceptional diastereomeric selectivities and consistently reproducible yields. These compounds are of significant interest due to their remarkable biological activities toward influenza endonuclease. Highly Diastereoselective Access to Densely Functionalized Piperidine Cores of Influenza Endonuclease Inhibitors via a Metal-Free S(N)1 Approach.,Zhang Y, Sun C, Guo L, Zhao K, Bennett F, Lam YH, Gao Q, Ruhl KE, Pirnot MT, Emmert MH, Hollenstein K, Eddins MJ, Su HP, Shao G, Song C, Lo MM, Peng F, Qi J, Crowley BM, McCauley JA, Price IR J Org Chem. 2025 Jan 17;90(2):1175-1179. doi: 10.1021/acs.joc.4c02379. Epub 2025 , Jan 2. PMID:39745425[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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