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By modifying the ester group and thus its susceptibility to esterase, and structural features critical to the lactonization rate, H<jats:sub>2<\/jats:sub>S release rates can be tuned. Such prodrugs directly release hydrogen sulfide without the involvement of perthiol species, which are commonly encountered with existing H<jats:sub>2<\/jats:sub>S donors. Additionally, such prodrugs can easily be conjugated to another non\u2010steroidal anti\u2010inflammatory agent, leading to easy synthesis of hybrid prodrugs. As a biological validation of the H<jats:sub>2<\/jats:sub>S prodrugs, the anti\u2010inflammatory effects of one such prodrug were examined by studying its ability to inhibit LPS\u2010induced TNF\u2010\u03b1 production in RAW 264.7 cells. This type of H<jats:sub>2<\/jats:sub>S prodrugs shows great potential as both research tools and therapeutic agents.<\/jats:p>","DOI":"10.1002\/anie.201511244","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T02:33:42Z","timestamp":1454034822000},"page":"4514-4518","source":"Crossref","is-referenced-by-count":181,"title":["Esterase\u2010Sensitive Prodrugs with Tunable Release Rates and Direct Generation of Hydrogen Sulfide"],"prefix":"10.1002","volume":"55","author":[{"given":"Yueqin","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta GA 30303-3083 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingchen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta GA 30303-3083 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaili","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta GA 30303-3083 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta GA 30303-3083 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vayou","family":"Chittavong","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta GA 30303-3083 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta GA 30303-3083 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,28]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-012-0873-4"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2425"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2011"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108581"},{"key":"e_1_2_2_6_2","first-page":"4","volume":"59","author":"Lowicka E.","year":"2007","journal-title":"Pharmacol. 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