{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shaffer KD"],"funding":["NMR","NICHD NIH HHS","NIA NIH HHS","mass spectrometers","University of Pennsylvania","NINDS NIH HHS","Age Related Neurodegenerative Disease Training Grant fellowship","NIH HHS","NIGMS NIH HHS"],"pagination":["e202500578"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12631007"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(22)"],"pubmed_abstract":["Fibrillar aggregation of α-synuclein (αS) is a hallmark of Parkinson's disease (PD) and related disorders, including multiple system atrophy (MSA) and dementia with Lewy bodies (DLB). Herein, the fibril interactions of two candidate positron emission tomography (PET) imaging ligands, M503 and HY-215, being developed for imaging of PD/DLB and MSA, respectively, are investigated. Photo-crosslinking mass spectrometry is used to determine the sites of their binding to in vitro fibrils, and Förster resonance energy transfer with fluorescently labeled proteins is used to analyze conformational changes in the disordered αS C-terminus. Taken together, these studies show that the MSA-selective PET lead, HY-215, interacts with the C-terminus, unlike the PD-selective lead M503. This study indicates that interactions with the often-ignored disordered regions of αS fibrils should be considered in the development of PET probes and other therapeutic small molecules."],"journal":["Chembiochem : a European journal of chemical biology"],"pubmed_title":["Interactions of Neurodegenerative Disease Positron Emission Tomography Imaging Probe Candidates with the C-Terminus of α-Synuclein Fibrils."],"pmcid":["PMC12631007"],"funding_grant_id":["F31 AG090063","S10 OD030460","R01 HD106051","T32 GM133398","NIH T32 AG000255","NSF CHE 1827457","U19 NS110456","NIH S10 OD030460","RF1 NS103873","T32 AG000255"],"pubmed_authors":["Pagar VV","Mach RH","Kim HJ","Kim HY","Lougee MG","Petersson EJ","Perez RM","Garcia BA","Shaffer KD"],"additional_accession":[]},"is_claimable":false,"name":"Interactions of Neurodegenerative Disease Positron Emission Tomography Imaging Probe Candidates with the C-Terminus of α-Synuclein Fibrils.","description":"Fibrillar aggregation of α-synuclein (αS) is a hallmark of Parkinson's disease (PD) and related disorders, including multiple system atrophy (MSA) and dementia with Lewy bodies (DLB). Herein, the fibril interactions of two candidate positron emission tomography (PET) imaging ligands, M503 and HY-215, being developed for imaging of PD/DLB and MSA, respectively, are investigated. Photo-crosslinking mass spectrometry is used to determine the sites of their binding to in vitro fibrils, and Förster resonance energy transfer with fluorescently labeled proteins is used to analyze conformational changes in the disordered αS C-terminus. Taken together, these studies show that the MSA-selective PET lead, HY-215, interacts with the C-terminus, unlike the PD-selective lead M503. This study indicates that interactions with the often-ignored disordered regions of αS fibrils should be considered in the development of PET probes and other therapeutic small molecules.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-05-19T03:20:45.964Z","creation":"2026-05-19T03:11:45.5Z"},"accession":"S-EPMC12631007","cross_references":{"pubmed":["41078085"],"doi":["10.1002/cbic.202500578"]}}