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hmily601木蟲 (正式寫手)
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[求助]
幫忙翻譯下�。ㄓ袡C(jī)化學(xué)）
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| Amphotericin B is the archetype for small molecules that form transmembrane ion channels. However, despite extensive study for more than five decades, even the most basic features of this channel structure and its contributions to the antifungal activities of this natural product have remained unclear. We herein report that a powerful series of functional group-deficient probes have revealed many key underpinnings of the ion channel and antifungal activities of amphotericin B. Specifically, in stark contrast to two leading models, polar interactions between mycosamine and carboxylic acid appendages on neighboring amphotericin B molecules are not required for ion channel formation, nor are these functional groups required for binding to phospholipid bilayers. Alternatively, consistent with a previously unconfirmed third hypothesis, the mycosamine sugar is strictly required for promoting a direct binding interaction between amphotericin B and ergosterol. The same is true for cholesterol. Synthetically deleting this appendage also completely abolishes ion channel and antifungal activities. All of these results are consistent with the conclusion that a mycosamine-mediated direct binding interaction between amphotericin B and ergosterol is required for both forming ion channels and killing yeast cells. The enhanced understanding of amphotericin B function derived from these synthesis-enabled studies has helped set the stage for the more effective harnessing of the remarkable ion channel-forming capacity of this prototypical small molecule natural product. |
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【答案】應(yīng)助回帖
★ ★
Mally89(金幣+2): 感謝應(yīng)助！~歡迎常來！~O(∩_∩)O~ 2011-06-17 20:25:06
hmily601(金幣+30, 翻譯EPI+1): 辛苦了�。�！ 2011-06-17 20:50:22
Mally89(金幣+2): 感謝應(yīng)助！~歡迎常來！~O(∩_∩)O~ 2011-06-17 20:25:06
hmily601(金幣+30, 翻譯EPI+1): 辛苦了�。�！ 2011-06-17 20:50:22
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兩性霉素B是那些形成跨膜離子通道的小分子的原型，然而，盡管廣泛的研究了五十多年，但是這種通道結(jié)構(gòu)的最基本特征以及該天然產(chǎn)物的對(duì)抑菌活性的貢獻(xiàn)仍不是很清楚。在此我們報(bào)道了一個(gè)強(qiáng)大官能團(tuán)缺失的探測器系列，該系列揭示了兩性霉素B抑菌活性和離子通道的許多關(guān)鍵基礎(chǔ)。特別的是附屬于鄰近兩性霉素B分子上的mycosamine（胺）和羧酸之間的極性相互作用不需要離子通道的形成，這與兩個(gè)領(lǐng) 先模型是完全相反的，這些官能團(tuán)也不需要綁定到磷脂雙分子層上。或者與早先未證明的第三個(gè)假設(shè)是一致的，mycosamine（胺）糖在促進(jìn)麥角甾醇和兩性霉素B直接結(jié)合互動(dòng)中是必須的，同樣對(duì)膽固醇也是這樣的。以合成方法拆除這種附屬物也能徹底地喪失其離子通道和抑菌活性，所有的這些與得到的結(jié)論是一致的，結(jié)論是在麥角甾醇和兩性霉素B以mycosamine（胺）為媒介的直接結(jié)合互動(dòng)中需要形成離子通道并殺死酵母細(xì)胞。關(guān)于兩性霉素B官能化的進(jìn)一步理解來自于這些合成功能研究，合成功能研究為這些典型的天然產(chǎn)物小分子更有效地利用異常離子通道形成能力提供了平臺(tái)。 |
2樓2011-06-17 16:42:19
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