臺灣博碩士論文加值系統

抗生素藥物的濫用造成多重抗藥性細菌的出現，使開發新型抗微生物藥物變得迫切需要。抗微生物胜肽被視為一類新的抗生素，其特徵包含了快速撲殺目標細胞的能力及顯著且廣譜的活性。在我們先前的研究中，MAP-04-03 被開發作為有效的抗微生物胜肽 (MIC= 5 μM)，但具有高溶血性 (70.7%)。為了增加其抗微生物活性並降低溶血的副作用，我們藉由置換MAP-04-03序列中數個胺基酸，設計出三個胜肽類似物 (JJ-01, JJ-02 及 JJ-03)。這些類似物藉由固相胜肽合成法合成、RP-HPLC純化，並以 MALDI-TOF 質譜技術鑑定。利用圓二色光譜及生物活性探討其結構活性關係。相較於MAP-04-03，JJ-01, JJ-02 及 JJ-03 的螺旋結構皆下降，JJ-01 的抗微生物活性和MAP-04-03相同 (MIC = 5μM)，JJ-02表現出最高的活性 ( MIC= 2.5μM )，JJ-03的抗微生物活性和MAP-04-03相同( MIC= 5μM )。JJ-01 及 JJ-03 的溶血性皆有些微降低，分別為46.2% 及 55.6%；而JJ-02則顯示出最低的溶血性 ( 3.4% )。在此研究中，JJ-02 成為進一步開發抗微生物藥劑的先導胜肽。

The extensive use of antibiotics in medicine results in the multidrug-resistance of bacteria, making the development of new antimicrobial agents an urgent need. Antimicrobial peptides (AMPs) are considered as a new class of antibiotics with characteristics including an ability to kill target cells rapidly and an unusually broad spectrum of activity. In our previous study, MAP-04-03 was discovered as a potent antimicrobial peptide (MIC= 5 μM), but showed high hemolytic activity (70.7%). In the current study, to increase its antimicrobial activity and reduce the hemolytic side effect, three peptides analogs of MAP-04-03 (JJ-01, JJ-02 and JJ-03) were designed by substitution of certain amino acids in its sequence. These peptide analogs were synthesized by solid phase method, purified by RP-HPLC and characterized by MALDI-TOF MS. Structure - activity relationships of these analogs were studied by using circular dichroism and biological assays. The content of helical structure in JJ-01, JJ-02 and JJ-03 was lower than that of MAP-04-03 and the antimicrobial activity of JJ-01 was the same as that of MAP-04-03 (MIC = 5 μM), JJ-02 exhibited the highest activity (MIC= 2.5 μM), while JJ-03 showed the same activity as MAP-0403 (MIC= 5 μM). The hemolytic activity of JJ-01 and JJ-03 decreased slightly (46.2% and 55.6%, respectively), while JJ-02 showed the lowest hemolytic activity (3.4%). The potent peptide JJ-02 with little hemolytic activity is promising and becomes the lead for further development of antimicrobial agents.

Contents__________________________________________________
List of Tables ¬¬-------------------------------------------------------------- 2
List of Figures -------------------------------------------------------------- 3
中文摘要 5
Abstract 6
Introduction 7
Materials and Methods 9
Results and Discussion 13
References 42

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