|
|
| Type |
Poster Presentation |
| Area |
Life Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 19일 (금요일) 11:00~12:30 |
| Code |
LIFE.P-366 |
| Subject |
12-meric promising novel peptide antibiotic candidate for the treatment of Gram-negative sepsis |
| Authors |
Jieun Kim, Yangmee Kim*
Department of Biotechnology, Konkuk University, Korea
|
| Abstract |
Papiliocin, isolated from the swallowtail buterfly Papilio Xuthus, shows low toxicity and high bacterial cell selectivity particularly against Gram negative bacteria. Tertiary structures have revealed that these residues are composed of an N-terminal amphipathic α-helix and a hydrophobic C-terminal α-helix linked by a hinge. We determined the essential length of the N‐terminal fragment of papiliocin necessary to retain its biological activity. The minimum inhibitory concentration values and cytotoxicity measurement revealed that a PapN‐12mer containing a three‐turn, amphipathic helix was the shortest peptide exhibiting antibacterial activity without cytotoxicity. Based on these results, we designed 12mer peptides derived from original sequence, to obtain more potent activity against multidrug resistant Gram-negative bacteria and to improve cell selectivity and anti-inflammatory properties. In a mouse sepsis model, especially, Pap12-6 significantly improved survival, reduced bacterial growth in organs, and reduced LPS and inflammatory cytokine levels in the serum and organs. Pap12-6 showed minimal cytotoxicity towards mammalian cells and controlled liver and kidney damage, proving its high bacterial selectivity. Our results suggest that Pap12-6 is a promising peptide antibiotic for the therapeutic treatment of Gram-negative sepsis via dual bactericidal and immunomodulatory effects on the host |
| E-mail |
za3524@konkuk.ac.kr |
|
123rd General Meeting of the KCS