{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:17:04Z","timestamp":1773951424912,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Foundation for Innovation","award":["CFI 42481"],"award-info":[{"award-number":["CFI 42481"]}]},{"name":"GlycoNET NCE","award":["AM6"],"award-info":[{"award-number":["AM6"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["DJV\/05426"],"award-info":[{"award-number":["DJV\/05426"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\/04910"],"award-info":[{"award-number":["RGPIN\/04910"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aspergillus fumigatus, a filamentous fungus, is an opportunistic pathogen and the major causative agent of the often-fatal disease, invasive aspergillosis (IA). Current treatments for IA are limited due to their high toxicity and\/or the emergence of drug resistance; therefore, a need exists for the development of new therapeutics to treat IA. The Kdnase produced by A. fumigatus plays a vital role in maintaining cell wall integrity. As there are no known Kdnases in humans, developing inhibitors of Kdnase from this fungal pathogen is a promising therapeutic approach. The rapid testing of enzymatic activity in a high-throughput screen of large chemical libraries can be an efficient way to find new small molecule lead compounds. Herein we show that a Kdn glycoside with a self-immolative cleavable aglycon is a practical and efficient substrate for a high throughput assay to identify Kdnase inhibitors. We optimized the activity assay and screened over 27,000 compounds from two bioactive chemical libraries as potential inhibitors, and we compared the hit compounds\u2019 potency towards Aspergillus terreus and Trichophyton rubrum Kdnases, two other fungal Kdnases. We validated a number of hits and these small molecules are potential leads for the development of novel therapeutics to treat invasive aspergillosis.<\/jats:p>","DOI":"10.1093\/glycob\/cwae094","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T12:17:19Z","timestamp":1732191439000},"source":"Crossref","is-referenced-by-count":1,"title":["A self-immolative Kdn-glycoside substrate enables high-throughput screening for inhibitors of Kdnases"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8187-4831","authenticated-orcid":false,"given":"Ali","family":"Nejatie","sequence":"first","affiliation":[{"name":"Department of Chemistry , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]},{"name":"Simon Fraser University , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7170-6754","authenticated-orcid":false,"given":"Cameron","family":"Proceviat","sequence":"additional","affiliation":[{"name":"Department of Chemistry , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]},{"name":"Simon Fraser University , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8869-9028","authenticated-orcid":false,"given":"Christina","family":"Gros","sequence":"additional","affiliation":[{"name":"Department of Chemistry , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]},{"name":"Simon Fraser University , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Steves","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Simon Fraser University , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7100-0874","authenticated-orcid":false,"given":"Margo M","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Simon Fraser University , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6897-5558","authenticated-orcid":false,"given":"David J","family":"Vocadlo","sequence":"additional","affiliation":[{"name":"Department of Chemistry , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]},{"name":"Simon Fraser University , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]},{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-6752","authenticated-orcid":false,"given":"Andrew J","family":"Bennet","sequence":"additional","affiliation":[{"name":"Department of Chemistry , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]},{"name":"Simon Fraser University , , 8888 University Drive, Burnaby, BC V5A 1S6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"issue":"26","key":"2025011406163281800_ref1","doi-asserted-by":"crossref","first-page":"7492","DOI":"10.1002\/anie.201500088","article-title":"Self-immolative spacers: kinetic aspects, structure-property relationships, and 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