{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Logviniuk D"],"funding":["Israel Science Foundation","Ministerio de Ciencia e Innovaci?n","?la Caixa? Foundation"],"pagination":["5965-5975"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8991007"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["144(13)"],"pubmed_abstract":["Each year, infections caused by fungal pathogens claim the lives of about 1.6 million people and affect the health of over a billion people worldwide. Among the most recently developed antifungal drugs are the echinocandins, which noncompetitively inhibit β-glucan synthase, a membrane-bound protein complex that catalyzes the formation of the main polysaccharide component of the fungal cell wall. Resistance to echinocandins is conferred by mutations in <i>FKS</i> genes, which encode the catalytic subunit of the β-glucan synthase complex. Here, we report that selective removal of the benzylic alcohol of the nonproteinogenic amino acid 3<i>S</i>,4<i>S</i>-dihydroxy-l-homotyrosine of the echinocandins anidulafungin and rezafungin, restored their efficacy against a large panel of echinocandin-r"],"journal":["Journal of the American Chemical Society"],"pubmed_title":["Benzylic Dehydroxylation of Echinocandin Antifungal Drugs Restores Efficacy against Resistance Conferred by Mutated Glucan Synthase."],"pmcid":["PMC8991007"],"funding_grant_id":["PGC2018-099921-B-I00","LCF/PR/HR21/00737","LCF/PR/GN18/50310010","179/19"],"pubmed_authors":["Jaber QZ","Kozer N","Dobrovetsky R","Ksiezopolska E","Gabaldon T","Fridman M","Logviniuk D","Carmeli S"],"additional_accession":[]},"is_claimable":false,"name":"Benzylic Dehydroxylation of Echinocandin Antifungal Drugs Restores Efficacy against Resistance Conferred by Mutated Glucan Synthase.","description":"Each year, infections caused by fungal pathogens claim the lives of about 1.6 million people and affect the health of over a billion people worldwide. Among the most recently developed antifungal drugs are the echinocandins, which noncompetitively inhibit β-glucan synthase, a membrane-bound protein complex that catalyzes the formation of the main polysaccharide component of the fungal cell wall. Resistance to echinocandins is conferred by mutations in <i>FKS</i> genes, which encode the catalytic subunit of the β-glucan synthase complex. Here, we report that selective removal of the benzylic alcohol of the nonproteinogenic amino acid 3<i>S</i>,4<i>S</i>-dihydroxy-l-homotyrosine of the echinocandins anidulafungin and rezafungin, restored their efficacy against a large panel of echinocandin-r","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-05T13:24:10.898Z","creation":"2025-04-05T13:24:10.898Z"},"accession":"S-EPMC8991007","cross_references":{"pubmed":["35347986"],"doi":["10.1021/jacs.2c00269"]}}