| Literature DB >> 35594650 |
Shuhei Kawamura1, Rachel L Palte2, Hai-Young Kim3, Josep Saurí3, Christopher Sondey4, My S Mansueto4, Michael D Altman2, Michelle R Machacek5.
Abstract
Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5'-cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5.Entities:
Keywords: Cyclonucleoside; Medicinal chemistry; Molecular modeling; Nucleoside; PRMT5; PRMT5 inhibitor; X-ray crystallography
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Year: 2022 PMID： 35594650 DOI： 10.1016/j.bmc.2022.116820
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641