抗菌胜肽存在許多生物體中，為先天性防禦系統中的重要分子，能抵禦各種病原體的入侵。 為了克服細菌對抗生素產生抗藥性的問題，抗菌胜肽被視為極具潛力發展成用以替代傳統抗生素的藥物，因其主要是以物理性作用力對細菌細胞膜進行破壞及分解而造成細菌的死亡，且有些具有多重殺菌機制，較不易產生抗藥性。然而，在發展及設計新的抗菌胜肽上仍缺乏有系統可循的設計規則，因此我們希望能設計一個由簡單重覆序列組成的抗菌胜肽，希望藉此歸納出設計高抗菌力以及低溶血性的抗菌胜肽的設計規則。

先前研究了PEM2 (KKWRWWLKALAKK)，此短鏈且富含色胺酸( Trp-rich)的抗菌胜肽，顯示其對革蘭氏陽性菌及陰性菌皆具有抗菌能力，且對人類紅血球具低溶血性，將此序列進一步修改成PEM2-W5K/A9W (KKWRKWLKWLAKK)，發現其抗菌力增加且仍維持低溶血性。因此在本次的研究中，我們根據PEM2及PEM2-W5K/A9W的研究結果，設計了一富含色胺酸和離胺酸的抗菌胜肽，序列中間含三個WLK的重複單位，而頭尾兩端則加上兩個Lys，命名為WLK (KKWLKWLKWLKKK)。與PEW2及PEM2-W5K/A9W相較，發現WLK的抗菌力以及對鹽的耐受度都較PEM2來得好，但比PEM2-W5K/A9W差，而三者則皆具低溶血性。為了進一步了解結構與抗菌活性之間的關係，我們運用二維核磁共振得知WLK與DPC微胞結合時於水溶液中的結構，發現其呈現α-螺旋結構且具有明顯的兩性(amphipathicity)特性。我們也運用了順磁遲豫增強效應( paramagnetic relaxation enhancement, PRE)的原理，以Gd(DTPA-BMA)及16-doxylstearic acid做為paramagnetic probe，探討胜肽與膜之間的位置以及深度。結果顯示抗菌胜肽埋入膜內較深，且與膜的接觸面較大者，具有較高抗菌力及較強的鹽耐受性，因此藉由增加與膜接觸的疏水面的疏水性，可能有助於設計出具高抗菌力的抗菌胜肽。

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