{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang HY"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["1443-1450"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10018702"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(12)"],"pubmed_abstract":["Ternatin-family cyclic peptides inhibit protein synthesis by targeting the eukaryotic elongation factor-1α. A potentially related cytotoxic natural product ('A3') was isolated from Aspergillus, but only 4 of its 11 stereocentres could be assigned. Here, we synthesized SR-A3 and SS-A3-two out of 128 possible A3 epimers-and discovered that synthetic SR-A3 is indistinguishable from naturally derived A3. Relative to SS-A3, SR-A3 exhibits an enhanced residence time and rebinding kinetics, as revealed by single-molecule fluorescence imaging of elongation reactions catalysed by eukaryotic elongation factor-1α in vitro. An increased residence time-stereospecifically conferred by the unique β-hydroxyl in SR-A3-was also observed in cells. Consistent with its prolonged duration of action, thrice-week"],"journal":["Nature chemistry"],"pubmed_title":["Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumour eEF1A antagonist SR-A3."],"pmcid":["PMC10018702"],"funding_grant_id":["R35 CA242986","T32 GM145460","R01 GM079238","R01 GM098859"],"pubmed_authors":["Yang H","Weber JF","Al-Khdhairawi AAQ","Blanchard SC","Oltion K","Tom H","Taunton J","Ruggero D","Holm M","Wang HY"],"additional_accession":[]},"is_claimable":false,"name":"Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumour eEF1A antagonist SR-A3.","description":"Ternatin-family cyclic peptides inhibit protein synthesis by targeting the eukaryotic elongation factor-1α. A potentially related cytotoxic natural product ('A3') was isolated from Aspergillus, but only 4 of its 11 stereocentres could be assigned. Here, we synthesized SR-A3 and SS-A3-two out of 128 possible A3 epimers-and discovered that synthetic SR-A3 is indistinguishable from naturally derived A3. Relative to SS-A3, SR-A3 exhibits an enhanced residence time and rebinding kinetics, as revealed by single-molecule fluorescence imaging of elongation reactions catalysed by eukaryotic elongation factor-1α in vitro. An increased residence time-stereospecifically conferred by the unique β-hydroxyl in SR-A3-was also observed in cells. Consistent with its prolonged duration of action, thrice-week","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-05-29T22:11:49.114Z","creation":"2025-05-29T22:11:49.114Z"},"accession":"S-EPMC10018702","cross_references":{"pubmed":["36123449"],"doi":["10.1038/s41557-022-01039-3"]}}