普昂疾病(prion disease)是一種腦神經退化疾病，於許多動物及人類都有發現，例如發生於牛群的狂牛病，發生於人類的庫賈氏症…等等，患者共同特徵為運動不協調性及在患者腦切片中發現有海綿狀空隙般的空洞。而其疾病的病原體為蛋白質，由自然態蛋白質(PrPC)轉變成非自然態蛋白質(PrPSc)，但是，其轉變機制仍是個謎。之前的研究已經發現如果加入單醣於大頰鼠普昂蛋白序列108-144則會對形成澱粉樣沈澱過程有所影響，如果加入□a-N-乙醯半乳醣胺(□a-GalNAc)會抑制澱粉樣沈澱的形成，但有趣的是□b-N-乙醯葡萄醣胺(□b-GlcNAc)卻沒有卻沒有如此大的影響，表示澱粉樣沈澱具有『單醣專一性』。為了更深入了解其影響原因，我們合成了兩個非自然的單醣胜肽(□b-N-乙醯半乳醣胺(□b-GalNAc)和□a-N-乙醯葡萄醣胺(□a-GlcNAc))。發現□a-殊碳醣異構物(□a-GalNAc,□a-GlcNAc)皆具有抑制澱粉樣沈澱的效用，但□-殊碳醣異構物卻沒有。並且由核磁共振光譜看出Ser-135和Arg-136附近的位置對形成澱粉樣沈澱具有相當的重要性。除此之外，我們還比較了磷酸化和醣化對對普昂胜肽構形及其形成澱粉樣沈澱的影響。

Prion disease is a neurodegenerative disorder. The prion formation, resulting from a structural conversion of the prion protein from the cellular form (PrPC) to the pathogenic isoform (PrPSc), is the culprit of the malady. A posttranslational process on the prion protein has been implicated in the prion formation during the development of prion disease. However, what the modification is and how the modification works remain elusive. It has been found that adding one single sugar on the prion peptide (sequence 108-144) can affect the structural conversion of the modified peptide and the following amyloid fibril formation. Interestingly, this effect is sugar-specific. Introducing an □a-GalNAc to Ser-135 of the prion peptide could suppress the fibrillization while adding a □b-GlcNAc did not yield the same effect. In order to understand the origin of the effect, we performed a series glycosylations with these two sugars and another two non-native isomers □b-GalNAc, and □a-GlcNAc and compared their effects on the fibrillization of the prion peptide. We found that the anomeric position is the origin of the inhibition. Either □a-GalNAc or □a-GlcNAc has more prominent effect on the conformational energy of the peptide and inhibits the assembly of the peptide to form amyloid. The NMR results showed that the region of Ser-135 and Arg-136 plays the critical point for amyloidogenesis. We also compared the influence of glycosylation and phosphorylation on fibrillization.

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