我們使用人類 Pin1蛋白質中一個位在N端上稱為 WW domain的胜肽，來當作研究立體電子效應應用在胜肽折疊與和配體結合能力的小蛋白模型。WW Domain具有緊密、三股且反平行的β-sheet結構；而高度保留在各種WW domain 37號胺基酸位置的 proline (P37)在結構上扮演重要的角色，原因在於P37會與某些殘基形成一個疏水核，是用來穩定 WW domain的重要關鍵。原始的 WW Domain中 P37的位相是傾向 Cγ–endo的環構形，我們使用(2S,4R)-4-hydroxy- proline (Hyp), (2S,4R)-4-fluoroproline (Flp), (2S,4R)-4-methoxyproline (Mop), (2S,4S)-4-hydroxyproline (hyp), (2S,4S)-4-fluoroproline (flp), and (2S,4S)-4- methoxyproline (mop)這些非天然的胺基酸衍生物進行取代，探討構形對於結構穩定性和與配體結合力之影響。在變溫實驗和化學變性量測實驗中，我們可以觀察到使用 flp取代的 WW flp37，較原始的 WW domain來得更穩定一些，其他的變異蛋白則較原胜肽不穩定。由此可以看出立體電子效應對於造成不同環構形在結構穩定上並不是主要因素。另外，WW domain可以與含有磷酸的 serine/ threonine-proline胜肽進行結合。我們用等溫滴定卡計 (ITC)測量 WW domain與含磷酸根的配體 VPRpTPVGY之間的結合親合力。在25 °C下，WW flp37的解離常數( Kd)較原始 WW domain來得低，但其他的變異 WW Domain胜肽則有較高的 Kd，顯示 flp可以穩定 WW domain，並且增強其與配體之結合能力。至於其他脯胺酸衍生物則會造成 WW domain結構較為鬆散且不穩定而降低甚至失去與配體之結合能力。

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