S-Space College of Education (사범대학) Dept. of Science Education (과학교육과) Chemistry (화학전공) Theses (Master's Degree_화학전공)
Proline hinged amphipathic α-helical peptide enhances synergistic antimicrobial activity with various antibiotics by perturbing outer membrane of gram-negative bacteria
프롤린으로 꺾인 양면성 알파나선구조 펩타이드의 그람 음성균 외막 섭동에 의한 다양한 항생제와의 시너지 항균효과 향상에 관한 연구
- Cho Yunhwa
- 사범대학 과학교육과
- Issue Date
- 서울대학교 대학원
- Proline hinged antimicrobial peptide; synergistic effect; Inner membrane demolishing; Outer membrane perturbing
- 학위논문 (석사)-- 서울대학교 대학원 : 과학교육과 화학전공, 2017. 2. 유재훈.
- The proline hinge is a frequently observed conformation in antimicrobial peptides with high α-helical propensity. Since it disrupts intra-molecular hydrogen bonding cascade, hinged peptides have lower α-helicity and significantly reduce membrane-disrupting ability of host cells, affording alleviated toxicity. Furthermore, some hinged peptides give improved bactericidal effects. Thus, specific proline hinge might be quite important for increasing selective antimicrobial activity. In order to address this matter, a small proline-scanning library was made by using amphipathic 14-aa long LK and KL model peptides that are comprised with lysine and leucine. After measuring minimum inhibitory concentrations against E.coli, S.aureus and hemolytic activity against red blood cell, the hinged peptides could be categorized into three groups. One group showed complete loss of hemolytic activity and antimicrobial activity against S. aureus, while retained activity against E.coli. Since these peptides show the anticipated selectivity, further investigation for peptides in the group was done. KL-L9P, one of the peptides, showed the best synergy with antibiotics, which were not used against gram-negative bugs because of impermeability of the drug against outer membrane. Sytox Green staining and NPN assay showed that the peptide mainly perturbs outer membrane, while it does not demolish or penetrate into inner membrane. Consequently, three important standards
weak hemolytic activity, high OM perturbing ability and weak IM demolishing ability are found and they might be important factors to design synergistic antimicrobial peptide.