{"doi":"10.1055/a-1509-5904","title":"Catalytic Synthesis of PEGylated EGCG Conjugates that Disaggregate Alzheimer’s Tau","abstract":"Abstract The naturally occurring flavonoid (–)-epigallocatechin gallate (EGCG) is a potent disaggregant of tau fibrils. Guided by the recent cryo-electron microscopy (cryoEM) structure of EGCG bound to fibrils of tau derived from an Alzheimer’s brain donor, methods to site-specifically modify the EGCG D-ring with aminoPEGylated linkers are reported. The resultant molecules inhibit tau fibril seeding by Alzheimer’s brain extracts. Formulations of aminoPEGylated EGCG conjugated to the (quasi)-brain-penetrant nanoparticle Ferumoxytol inhibit seeding by AD-tau with linker length affecting activity. The protecting group-free catalytic cycloaddition of amino azides to mono-propargylated EGCG described here provides a blueprint for access to stable nanoparticulate forms of EGCG potentially useful as therapeutics to eliminate Alzheimer’s-related tau tangles.","journal":"Synthesis","year":2021,"id":196942,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":770189,"name":"Patrick G. Harran","orcid":"0000-0001-8748-5167","position":1,"is_corresponding":false},{"id":770850,"name":"Anton El Khoury","orcid":null,"position":2,"is_corresponding":false},{"id":473677,"name":"Paul M. Seidler","orcid":"0000-0001-8530-7244","position":3,"is_corresponding":false},{"id":225464,"name":"David Eisenberg","orcid":"0000-0003-2432-5419","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-18T23:50:19.568641Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}