{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["17(1)"],"submitter":["Zhang R"],"pubmed_abstract":["For targeted covalent protein modification at low-reactivity aspartates and glutamates, new methods are in high demand. We report a technique inspired by the HaloTag technology, which employs nucleophilic substitution at chloroalkane-functionalised ligands by a specific aspartate residue. Embedding of alkyl bromide warheads into non-covalent inhibitors enables covalent modification of a glutamate in the lipoprotein binding chaperone - phosphodiesterase of retinal rod subunit delta (PDEδ), which shuttles prenylated lipoproteins between cellular membranes and thereby mediates their activity. Its hydrophobic ligand-binding pocket contains p.E88 as the only accessible nucleophile for covalent targeting. We show that a covalent inhibitor, termed DeltaTag, overcomes limitations of non-covalent i"],"journal":["Nature communications"],"pagination":["1257"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12864978"],"repository":["biostudies-literature"],"pubmed_title":["Covalent modification of a glutamic acid inspired by HaloTag technology."],"pmcid":["PMC12864978"],"pubmed_authors":["Gasper R","Liu J","Waldmann H","Kaschani F","Janning P","Zhang R","Unger A","Kaiser M"],"additional_accession":[]},"is_claimable":false,"name":"Covalent modification of a glutamic acid inspired by HaloTag technology.","description":"For targeted covalent protein modification at low-reactivity aspartates and glutamates, new methods are in high demand. We report a technique inspired by the HaloTag technology, which employs nucleophilic substitution at chloroalkane-functionalised ligands by a specific aspartate residue. Embedding of alkyl bromide warheads into non-covalent inhibitors enables covalent modification of a glutamate in the lipoprotein binding chaperone - phosphodiesterase of retinal rod subunit delta (PDEδ), which shuttles prenylated lipoproteins between cellular membranes and thereby mediates their activity. Its hydrophobic ligand-binding pocket contains p.E88 as the only accessible nucleophile for covalent targeting. We show that a covalent inhibitor, termed DeltaTag, overcomes limitations of non-covalent i","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-07-15T06:32:23.416Z","creation":"2026-06-30T03:21:58.745Z"},"accession":"S-EPMC12864978","cross_references":{"pubmed":["41617704"],"doi":["10.1038/s41467-026-68999-9"]}}