{"doi":"10.1080/14756366.2020.1781107","title":"Design, synthesis, and <i>in vitro</i> evaluation of aza-peptide aldehydes and ketones as novel and selective protease inhibitors","abstract":"Aza-peptide aldehydes and ketones are a new class of reversible protease inhibitors that are specific for the proteasome and clan CD cysteine proteases. We designed and synthesised aza-Leu derivatives that were specific for the chymotrypsin-like active site of the proteasome, aza-Asp derivatives that were effective inhibitors of caspases-3 and -6, and aza-Asn derivatives that inhibited S. mansoni and I. ricinus legumains. The crystal structure of caspase-3 in complex with our caspase-specific aza-peptide methyl ketone inhibitor with an aza-Asp residue at P1 revealed a covalent linkage between the inhibitor carbonyl carbon and the active site cysteinyl sulphur. Aza-peptide aldehydes and ketones showed no cross-reactivity towards cathepsin B or chymotrypsin. The initial in vitro selectivity of these inhibitors makes them suitable candidates for further development into therapeutic agents to potentially treat multiple myeloma, neurodegenerative diseases, and parasitic infections.","journal":"Journal of Enzyme Inhibition and Medicinal Chemistry","year":2020,"id":88311,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":447642,"name":"Leilani Lotti Díaz","orcid":"0000-0001-5955-9595","position":1,"is_corresponding":false},{"id":447643,"name":"Sarah E. Border","orcid":"0000-0001-5739-3093","position":2,"is_corresponding":false},{"id":448506,"name":"Steven C. Ratigan","orcid":null,"position":3,"is_corresponding":false},{"id":448507,"name":"Kayla Q. Kasper","orcid":null,"position":4,"is_corresponding":false},{"id":447644,"name":"Daniel Sojka","orcid":"0000-0002-9848-9435","position":5,"is_corresponding":false},{"id":447645,"name":"Pavla Fajtová","orcid":"0000-0002-4029-0706","position":6,"is_corresponding":false},{"id":241386,"name":"Conor R. Caffrey","orcid":"0000-0003-3048-8572","position":7,"is_corresponding":false},{"id":90292,"name":"Guy S. Salvesen","orcid":"0000-0002-7933-6732","position":8,"is_corresponding":false},{"id":328851,"name":"Craig A. McElroy","orcid":"0000-0001-5950-0120","position":9,"is_corresponding":false},{"id":447646,"name":"Christopher M. Hadad","orcid":"0000-0003-1211-4315","position":10,"is_corresponding":false},{"id":447647,"name":"Özlem Doǧan Ekici","orcid":"0000-0002-1237-1269","position":11,"is_corresponding":false},{"id":447641,"name":"Thomas S. Corrigan","orcid":"0000-0001-5113-9406","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T22:00:56.736935Z","pmid":"32633155","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":[]}