Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/35193
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dc.contributor.authorLin, Ming-Chengen_US
dc.contributor.authorLin, Gin-Zenen_US
dc.contributor.authorHwang, Ching-Inen_US
dc.contributor.authorJian, Shuo-Yungen_US
dc.contributor.authorLin, Jamesen_US
dc.contributor.authorShen, Yu-Fongen_US
dc.contributor.authorLin, Gialihen_US
dc.date2012-07zh_TW
dc.date.accessioned2014-06-06T07:48:55Z-
dc.date.available2014-06-06T07:48:55Z-
dc.identifier.urihttp://hdl.handle.net/11455/35193-
dc.description.abstract1,3,5-Tri-N-alkylcarbamylphloroglucinols (1–4) are synthesized as conformationally constrained analogs of triacylglycerols (TGs) to probe Jenck’s proximity effect in the cholesterol esterase inhibition. For the cholesterol esterase inhibition, inhibitors 1–4 are 220–760-fold more potent than 1,2,3-tri-N-alkylcarbamylglycerols (13–15) that are substrate analogs of TG. Comparison of tridentate inhibitors 1–4, bidentate inhibitors 3,5-di-N-n-alkylcarbamyloxyphenols (5–8) and monodentate inhibitors 5-N-n-alkylcarbamyloxyresorcinols (9–12) indicates that inhibitory potencies are as followed: tridentate inhibitor > bidentate inhibitor > monodentate inhibitor. The log ki and pKi values of tridentate inhibitors, bidentate inhibitors, and monodentate inhibitors are linearly correlated with the alkyl chain length indicating a common mechanism in each inhibition. Also, positive slopes of these correlations indicate that the longer chain inhibitors bind more tightly to the enzyme than the shorter ones. Molecular dockings of tridentate 1, bidentate 5, and monodentate 9 into the X-ray crystal structure of cholesterol esterase suggest that one carbamyl group in the cis form of the inhibitor binds to the acyl chain-binding site of the enzyme. The second carbamyl groups in the trans forms of inhibitors 1 and 5 bind to the second acyl chainbinding site of the enzyme. The third carbamyl group in the trans form of inhibitor 1 binds to the third acyl chain-binding site of the enzyme. Moreover, the configuration of the inhibitor in the enzyme-inhibitor complex is the (1,3,5)-(cis, trans, trans)-tricarbamate form that mimics the (1gauche, 2gauche)-conformation of TG.en_US
dc.language.isoen_USzh_TW
dc.relationPROTEIN SCIENCE, Volume 21, page(s) 1344—1357.en_US
dc.relation.urihttp://dx.doi.org/10.1002/pro.2121en_US
dc.subjectcholesterol esteraseen_US
dc.subjectinhibitorsen_US
dc.subjectcarbamatesen_US
dc.subjectmolecular dockingen_US
dc.titleSynthesis and evaluation of a new series of tri-, di-, and mono-Nalkylcarbamylphloroglucinols as conformationally constrained inhibitors of cholesterol esteraseen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1002/pro.2121zh_TW
dc.contributor.catalogerWei Chun Wangen_US
item.openairetypeJournal Article-
item.fulltextno fulltext-
item.grantfulltextnone-
item.languageiso639-1en_US-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
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