{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chaudhuri S"],"funding":["Wellcome Leap","Department for Science, Innovation and Technology","Royal Academy of Engineering","Wellcome Trust","Engineering and Physical Sciences Research Council"],"pagination":["7687-7697"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11480980"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["64(19)"],"pubmed_abstract":["Myotonic dystrophy type I (DM1) is the most common form of adult muscular dystrophy and is a severe condition with no treatment currently available. Recently, small-molecule ligands have been developed as targeted covalent inhibitors that have some selectivity for and covalently inhibit cyclin-dependent kinase 12 (CDK12). CDK12 is involved in the transcription of elongated RNA sections that results in the DM1 condition. The covalent bond is achieved after nucleophilic addition to a Michael acceptor warhead. Previous studies of the conformational preferences of thio-Michael additions have focused on characterizing the reaction profile based on the distance between the sulfur and β-carbon atoms. Rotamerism, however, has not been investigated extensively. Here, we use high-level quantum chemi"],"journal":["Journal of chemical information and modeling"],"pubmed_title":["Quantum Chemical Characterization of Rotamerism in Thio-Michael Additions for Targeted Covalent Inhibitors."],"pmcid":["PMC11480980"],"funding_grant_id":["CiET2021_17","Q4Bio-2023-4424538316","EP/W028131/1"],"pubmed_authors":["Hayes CJ","Chaudhuri S","Rogers DM","Hirst JD","Inzani K"],"additional_accession":[]},"is_claimable":false,"name":"Quantum Chemical Characterization of Rotamerism in Thio-Michael Additions for Targeted Covalent Inhibitors.","description":"Myotonic dystrophy type I (DM1) is the most common form of adult muscular dystrophy and is a severe condition with no treatment currently available. Recently, small-molecule ligands have been developed as targeted covalent inhibitors that have some selectivity for and covalently inhibit cyclin-dependent kinase 12 (CDK12). CDK12 is involved in the transcription of elongated RNA sections that results in the DM1 condition. The covalent bond is achieved after nucleophilic addition to a Michael acceptor warhead. Previous studies of the conformational preferences of thio-Michael additions have focused on characterizing the reaction profile based on the distance between the sulfur and β-carbon atoms. Rotamerism, however, has not been investigated extensively. Here, we use high-level quantum chemi","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-04T07:40:45.766Z","creation":"2025-04-04T07:40:45.766Z"},"accession":"S-EPMC11480980","cross_references":{"pubmed":["39265068"],"doi":["10.1021/acs.jcim.4c01379"]}}