| Summary: | 碩士 === 東海大學 === 化學系 === 104 === Development of new classes of antimicrobial agents is urgent because widely used antibiotics had caused antibiotics-resistance bacteria. As antimicrobial peptides can penetrate into the cell membrane, decomposed by enzymes, and then absorbed, they do not cause resistance easily. Antimicrobial peptides not only exhibit antimicrobial activity but also show selectivity or specificity, therefore, antimicrobial peptides has become alternative antibiotics and potential antimicrobial agents. Recently, we reported a peptide, MAP-04-04 (KRLRRVWRRWR) which is an analog of antimicrobial peptide Ixosin-B-amide (QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY) and exhibited antibacterial activity but very low hemolytic effect. The aim of this study is to develop poteny antibacterial peptides derivatives of MAP-04-04 with enhanced specificity and least site effect and to identify novel antimicrobial cyclic peptides by high-throughput synhesis of combinatorial cyclic peptide libraries and screening of their antimicrobial activities. A series of N-methylated and cyclic peptide analogs of MAP-04-04 were designed and synthesized by solid phase method, purified by RP-HPLC, and characterized by MALDI-TOF-MS. The results of MIC90 indicated that antimicrobial activities of MAP-04-04-LM-C against E. coli, S. aureus, and P. aeruginosa were 20 μM, 10 μM, and 5 μM, respectively. Antimicrobial activities of MAP-04-04-LM against E. coli, S. aureus, and P. aeruginosa were 20 μM, 10 μM, and 10 μM, respectively. Antimicrobial activities of MAP-04-04-LL against E. coli, S. aureus, and P. aeruginosa were 20 μM, 5 μM, and 5 μM, respectively. Overall, MAP-04-04-LL exhibits the best antimicrobial activity among these peptide analogs and is our current lead peptide for the development of antimicrobial agents.
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