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Selected TPDs are also potently bioactive against the causative agent of human African trypanosomiasis, <jats:italic>Trypanosoma brucei<\/jats:italic>, both <jats:italic>in\u2005vitro<\/jats:italic> and <jats:italic>in\u2005vivo<\/jats:italic>. So far, however, there has been no direct evidence of tubulin engagement by these TPDs in <jats:italic>T. brucei<\/jats:italic>. Therefore, to enable further investigation of anti\u2010trypanosomal TPDs, a TPD derivative amenable to photoaffinity labeling (PAL) was designed, synthesized, and evaluated in PAL experiments using HEK293 cells and <jats:italic>T. brucei<\/jats:italic>. The data arising confirmed specific labeling of <jats:italic>T. brucei<\/jats:italic> tubulin. In addition, proteomic data revealed differences in the labeling profiles of tubulin between HEK293 and <jats:italic>T. brucei<\/jats:italic>, suggesting structural differences between the TPD binding site(s) in mammalian and trypanosomal tubulin.<\/jats:p>","DOI":"10.1002\/cmdc.202300656","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T11:58:30Z","timestamp":1706270310000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Design, Synthesis, and Evaluation of An Anti\u2010trypanosomal [1,2,4]Triazolo[1,5\u2010<i>a<\/i>]pyrimidine Probe for Photoaffinity Labeling Studies"],"prefix":"10.1002","volume":"19","author":[{"given":"Bobby","family":"Lucero","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California, San Diego  9500 Gilman Drive La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol R.","family":"Francisco","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California, San Diego  9500 Gilman Drive La Jolla CA 92093 USA"},{"name":"Center for Discovery and Innovation in Parasitic Diseases Skaggs School of Pharmacy and Pharmaceutical Sciences University of California, San Diego  9500 Gilman Drive La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Varricchio","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Cardiff University  Cardiff CF103NB U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California, San Diego  9500 Gilman Drive La Jolla CA 92093 USA"},{"name":"Center for Discovery and Innovation in Parasitic Diseases Skaggs School of Pharmacy and Pharmaceutical Sciences University of California, San Diego  9500 Gilman Drive La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuemang","family":"Yao","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine University of Pennsylvania  3600 Spruce Street Philadelphia Pennsylvania 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Brancale","sequence":"additional","affiliation":[{"name":"Vysok\u00e1 \u0160kola Chemicko-Technologick\u00e1 v Praze Department of Organic Chemistry  Technick\u00e1 5 Prague 16628 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R.","family":"Brunden","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine University of Pennsylvania  3600 Spruce Street Philadelphia Pennsylvania 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor R.","family":"Caffrey","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases Skaggs School of Pharmacy and Pharmaceutical Sciences University of California, San Diego  9500 Gilman Drive La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-3850","authenticated-orcid":false,"given":"Carlo","family":"Ballatore","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases Skaggs School of Pharmacy and Pharmaceutical Sciences University of California, San Diego  9500 Gilman Drive La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.231175"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01411"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01605"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.05.016"},{"key":"e_1_2_8_5_1","volume":"7","author":"Yang J.","year":"2021","journal-title":"Sci. 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