{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:31:09Z","timestamp":1790627469640,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,1,19]],"date-time":"2012-01-19T00:00:00Z","timestamp":1326931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>Disruption of glycosylphosphatidylinositol biosynthesis is genetically and chemically validated as a drug target against the protozoan parasite <jats:italic>Trypanosoma brucei<\/jats:italic>, the causative agent of African sleeping sickness. The <jats:italic>N<\/jats:italic>\u2010acetylglucosamine\u2010phosphatidylinositol de\u2010<jats:italic>N<\/jats:italic>\u2010acetylase (deNAc) is a zinc metalloenzyme responsible for the second step of glycosylphosphatidylinositol biosynthesis. We recently reported the synthesis of eight deoxy\u20102\u2010<jats:italic>C<\/jats:italic>\u2010branched monosaccharides containing carboxylic acid, hydroxamic acid, or <jats:italic>N<\/jats:italic>\u2010hydroxyurea substituents at the C2 position that may act as zinc\u2010binding groups. Here, we describe the synthesis of a glucocyclitol\u2010phospholipid incorporating a hydroxamic acid moiety and report the biochemical evaluation of the monosaccharides and the glucocyclitol\u2010phospholipid as inhibitors of the trypanosome deNAc in the cell\u2010free system and against recombinant enzyme. Monosaccharides with carboxylic acid or hydroxamic acid substituents were found to be the inhibitors of the trypanosome deNAc with IC<jats:sub>50<\/jats:sub> values 0.1\u20131.5\u2003m<jats:sc>m<\/jats:sc>, and the glucocyclitol\u2010phospholipid was found to be a dual inhibitor of the deNAc and the \u03b11\u20104\u2010mannose transferase with an apparent IC<jats:sub>50<\/jats:sub>\u2003=\u200319\u2003\u00b1\u20030.5\u2003\u03bc<jats:sc>m<\/jats:sc>.<\/jats:p>","DOI":"10.1111\/j.1747-0285.2011.01300.x","type":"journal-article","created":{"date-parts":[[2011,12,16]],"date-time":"2011-12-16T14:48:06Z","timestamp":1324046886000},"page":"270-278","source":"Crossref","is-referenced-by-count":8,"title":["Inhibitors Incorporating Zinc\u2010Binding Groups Target the GlcNAc\u2010PI de\u2010<i>N<\/i>\u2010acetylase in <i>Trypanosoma brucei<\/i>, the Causative Agent of African Sleeping Sickness"],"prefix":"10.1111","volume":"79","author":[{"given":"Nuha Z.","family":"Abdelwahab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur T.","family":"Crossman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A. J.","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Urbaniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,19]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1242\/jcs.112.17.2799","article-title":"The structure, biosynthesis and function of glycosylphosphatidyl inositol anchors, and the contributions of trypanosome research","volume":"112","author":"Ferguson M.A.J.","year":"1999","journal-title":"J Cell Sci"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.180230697"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208374200"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E02-03-0167"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600456"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950180406"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(97)00187-4"},{"key":"e_1_2_7_9_2","volume-title":"African Trypanosomiasis","author":"World Health Organisation","year":"2001"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(99)00058-7"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(00)00151-4"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10254"},{"key":"e_1_2_7_13_2","doi-asserted-by":"crossref","first-page":"11168","DOI":"10.1016\/S0021-9258(18)60444-2","article-title":"Biosynthesis of the glycerol phosphatidylinositol membrane anchor of the trypanosome variant surface glycoprotein","volume":"264","author":"Doering T.L.","year":"1989","journal-title":"J Biol Chem"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3280171"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.11.6476"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/9.4.415"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.21.5922"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.13.3322"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi000854w"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203371200"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2008.00688.x"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb800143w"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502402200"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867023369402"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043364018"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carres.2008.03.028"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carres.2011.02.004"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6215(02)00187-8"},{"key":"e_1_2_7_29_2","volume-title":"GPI Membrane Anchors: Isolation and Analysis","author":"Ferguson M.A.J.","year":"1994"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo0109220"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90241-6"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo951711w"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9734814"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-6215(90)84021-L"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/0470053488"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo970903j"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(02)00131-X"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1747-0285.2011.01300.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1747-0285.2011.01300.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/j.1747-0285.2011.01300.x","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1747-0285.2011.01300.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T06:35:59Z","timestamp":1697265359000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1747-0285.2011.01300.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,19]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1111\/j.1747-0285.2011.01300.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1747-0285.2011.01300.x","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,19]]}}}