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파아지디스플레이 기법을 이용한 새로운 TLR4/MD2 라이간드 규명
- Alternative Title
- Cho Hey-young
- Author(s)
- Cho, Hey Young
- Alternative Author(s)
- Cho Hey-young
- Advisor
- 최상돈
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2014-02
- Language
- eng
- Keyword
- TLR4; phage display; antagonist; agonist
- Alternative Abstract
- The novel ligands of human Toll-like receptors (TLRs) can act as a vaccine adjuvant and therapeutic agent for sepsis and inflammatory diseases. We identified two peptide sequences based on their binding affinity to TLR4/MD2 complex by utilizing phage-display random peptide library and bio-panning technology. Selected peptides tend to be directed to biologically relevant sites on the surface of the target protein. After several rounds of phage screening, the phage output ratio was even higher than the first round by 15-mer and 12-mer peptide library phages. After bio-panning, it has been found that a number of phage clones indicated a consensus sequence of 15-mer peptides, which has been named Ajou01. This peptide antagonized LPS-induced activation of nuclear factor (NF)-κB in human embryonic kidney (HEK)-Blue hTLR4 cells as well as nuclear translocation of NF-κB in mice macrophages. Furthermore, this peptide hinders expression of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 in mice macrophages. Another 12-mer peptide, after bio-panning has been found out, which was named Ajou02. When treated the HEK-Blue hTLR4 cells, it has been observed that this peptide triggers a weak immune response. The property of Ajou02 to weakly initiate immune response can be a candidate for adjuvants in vaccine preparation where ordinary LPS cannot be used owing to their lethal effects. These findings suggest that Ajou01 and Ajou02 have therapeutic potential and, can be validated in inflammatory and immune related disorders.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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