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Conversion of antimicrobial peptides toward cell penetrating peptides : 항균 펩타이드에서 세포 투과 펩타이드로의 전환 :
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- Authors
- Advisor
- 유재훈
- Major
- 사범대학 과학교육과
- Issue Date
- 2016-02
- Publisher
- 서울대학교 대학원
- Keywords
- 항균 펩타이드 ; 세포 투과 펩타이드 ; 용혈 현상
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 사범대학 과학교육과, 2016. 2. 유재훈.
- Abstract
- Higher vertebrates produce antimicrobial peptides (AMPs) as a result of immune response and main mode of action for AMPs is disrupting the membrane. However, penetration of AMPs into cells followed by interact with intracellular targets might be other mechanism. They also have severe toxicity that might come from disruption of eukaryotic membrane as well as modulation of internal targets through membrane translocation. Though AMPs have both membrane disrupting and penetrating mechanism simultaneously, we tried to make and select mutant(s) in which cell disrupting ability is deleted but the penetrating ability is left over among systematically mutants peptide(s) from an amphipathic α-helical model peptide, sequenced as LKKLLKLLKKLLKLAG. Most of mutants showed correlations between their cell penetrating ability and cell disrupting ability. In contrast, L8Q- and L8K-mutants in which hydrophobic interactions are ruined by hydrophilic groups in Q or K showed cell penetrating ability at low micromolar concentrations, while their membrane disrupting ability were totally abolished. Mutant peptides with unnatural amino acids with shorter and longer carbon chains of Q- and K-analogues were also generated and their membrane disrupting and penetrating abilities were also investigated. While longer carbon chain (homoQ and homoK) mutants gave similar cell penetrating ability, shorter carbon chain mutants (N, Dab and Orn) showed total loss of cell penetrating ability as well as membrane demolishing ability. MTX-conjugated peptides of all cell penetrating peptides selected (Q and K) gave much severe toxicity in comparison with the corresponding non-conjugated mutants, suggesting that internalized MTX might be a culprit of toxicity. Positional Q- and K-mutation of a natural AMP, LL37, gave total loss of cell disrupting ability while be left cell penetrating ability. Taken together, Q and K mutation might be a strategy in nature to be left over the cell penetrating ability while deleting membrane disrupting ability of AMPs.
- Language
- English
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