{"doi":"10.1021/acs.orglett.3c02130","title":"Development of a <i>p</i>-Hydroxybenzyl-Alcohol-Linked Glutamate Prodrug for Activation by <i>Pseudomonas</i> Carboxypeptidase G2","abstract":"Directed enzyme–prodrug therapies used for targeted drug delivery require prodrugs that are chemically stable and processed efficiently by the activating enzyme. We recently reported the development of AMS-6-Glu ( 2 ), a glutamate-masked version of the cytotoxic natural product 5′- O -sulfamoyladenosine (AMS, 1 ) that can be activated by Pseudomonas carboxypeptidase G2 (CPG2). Herein, we report the development of a second-generation prodrug, AMS-5′-PHOBA-Glu ( 5 ), that undergoes cleavage by CPG2 with >160-fold higher efficiency. Use of a p -hydroxybenzyl alcohol (PHOBA) self-immolative linker overcame unexpected chemical instability observed with a conventional p -aminobenzyl alchohol (PABA) linker.","journal":"Organic Letters","year":2023,"id":373310,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":638886,"name":"Broderick C. Corless","orcid":"0000-0002-9125-1803","position":1,"is_corresponding":false},{"id":646214,"name":"Thomas J. Gardner","orcid":"0000-0003-0838-8751","position":2,"is_corresponding":false},{"id":255865,"name":"David A. Scheinberg","orcid":"0000-0002-4160-923X","position":3,"is_corresponding":false},{"id":274354,"name":"Derek S. Tan","orcid":"0000-0002-7956-9659","position":4,"is_corresponding":false},{"id":1134637,"name":"Joohoon Lee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T01:16:02.217046Z","pmid":"37602700","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":[]}