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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/33815

Title: 以Echinocandin B為基礎結構合成的環狀胜太篩選抗黴藥物抑制致病性酵母菌1,3-B-聚多葡萄糖的合成
Authors: 柯源悌
Contributors: 國立臺灣海洋大學:食品科學系
Keywords: 致病性酵母菌;抗真菌劑;環狀胜?;葡萄糖合成
Pathogenic yeast;Antifungal agent;Cyclopeptide;Glucose synthesis;Echinocandin B
Date: 1998-11
Issue Date: 2013-06-07T06:18:01Z
Publisher: 行政院國家科學委員會
Abstract: 摘要:本計畫執行期間完成酵母菌及念珠菌種包括S. cerevisiae,C. albicans,C. kefyr,C. glabrata,C. lustianiae等株種培養,生長曲線之確立,其細胞膜微粒體的製備,以14C標幟基質的放射性法測試出其1,3-.beta.-Glucan Synthase(GS)的活性,並對以固相胜?合成法(Solid phase peptide synthesis)中Fmoc/tBu chemistry之合成方法,配合醯化反應,合成數種Echinocandin衍生之月生月太化合物作抗黴活性測試,包括Aromatic-N-Orn-Thr-Pro-Tyr-Thr-Pro-COOH 及NH2-Orrn-Thr-Pro-Tyr-Thr-Pro-COOH等;如預期結果,Echinocandin衍生之月生月太 化合物對多株胞膜微粒體的GS活性有抑制,因此得以利用SPR(Surface plasmon resonance)從事Echinocandin衍生之胜?化合物對GS酵素抑制機制的探討;除此以外,由本校藥化所郭盛助教授實驗室獲得一批CCY衍生化合物,篩選對GS酵素活性的抑制發現對官能基具有選擇性,因此對抑制機制的探討及潛力Echinocandin類抗黴藥物的設計將有正面意義。
Abstract:Yeast strains S. cerevisiae, C. albicans, C. kefyr, C. glabrata, C. lustianiae were selected to conduct activity test for Echinocandin-based cyclopeptide compounds. Tested peptides were synthesized by solid phase Fmoc/tBu chemistry and acylation. Yeast growth curves were certained, their microsomal membranes were prepared and their 1,3-.beta.-glucan synthase (GS) activities were measured by 14C-labeled substrate incorporation radioassay. The antifungal activity of synthetic Echinocandin-based cyclopeptide compounds including aromatic-N-Orn-Thr-Pro-Tyr-Thr-Pro-COOH and NH2-Orrn-Thr-Pro-Tyr-Thr-Pro-COOH were tested and found to be active against microsomal GS activity of several pathogenic yeast strains. SPR (Surface Plasmon Resonance) technology was used to study GS inhibition mechanism of Echinocandin derived peptides. Besides, a group of CCY derivatives from Dr. Sheng-Chu Kuo were also screened for antifungal activity and found to perform structural selectivity against GS activity; which highlights GS targeted antifungal inhibition mechanism as well as potential Echinocandin-based antifungal drug design.
Relation: NSC88-2314-B039-034
URI: http://ntour.ntou.edu.tw/handle/987654321/33815
Appears in Collections:[食品科學系] 研究計畫

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