PMID- 23594231 OWN - NLM STAT- MEDLINE DCOM- 20130709 LR - 20221207 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 56 IP - 9 DP - 2013 May 9 TI - Structure and function of a potent lipopolysaccharide-binding antimicrobial and anti-inflammatory peptide. PG - 3546-56 LID - 10.1021/jm4004158 [doi] AB - Antimicrobial peptides (AMPs) play pivotal roles in the innate defense of vertebrates. A novel AMP (cathelicidin-PY) has been identified from the skin secretions of the frog Paa yunnanensis . Cathelicidin-PY has an amino acid sequence of RKCNFLCKLKEKLRTVITSHIDKVLRPQG. Nuclear magnetic resonance (NMR) spectroscopy analysis revealed that cathelicidin-PY adopts a tertiary structure with a mostly positively charged surface containing a helix (Thr15-Ser19). It possesses strong antimicrobial activity, low hemolytic activity, low cytotoxicity against RAW 264.7 cells, and strong anti-inflammatory activity. The action of antimicrobial activity of cathelicidin-PY is through the destruction of the cell membrane. Moreover, cathelicidin-PY exerts anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and inflammatory cytokines such as tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Cathelicidin-PY inhibits the activation of Toll-like receptor 4 (TLR4) inflammatory response pathways induced by lipopolysaccharide (LPS). The NMR titration experiments indicated that cathelicidin-PY can bind to LPS. In conclusion, we have identified a novel potent peptide antibiotic with both antimicrobial and anti-inflammatory activities and laid the groundwork for future research and development. FAU - Wei, Lin AU - Wei L AD - Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China. FAU - Yang, Juanjuan AU - Yang J FAU - He, Xiaoqin AU - He X FAU - Mo, Guoxiang AU - Mo G FAU - Hong, Jing AU - Hong J FAU - Yan, Xiuwen AU - Yan X FAU - Lin, Donghai AU - Lin D FAU - Lai, Ren AU - Lai R LA - eng SI - GDB/2LR7 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130429 PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 0 (Anti-Infective Agents) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Solutions) RN - 31C4KY9ESH (Nitric Oxide) RN - 0 (Cathelicidins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Anti-Infective Agents/*chemistry/metabolism/*pharmacology/toxicity MH - Anti-Inflammatory Agents/*chemistry/metabolism/*pharmacology/toxicity MH - Antimicrobial Cationic Peptides/*chemistry/metabolism/*pharmacology/toxicity MH - Anura MH - Bacteria/drug effects MH - Base Sequence MH - Cell Line MH - Cytokines/biosynthesis MH - Female MH - Fungi/drug effects MH - Hemolysis/drug effects MH - Humans MH - Lipopolysaccharides/*metabolism/pharmacology MH - Male MH - Mice MH - Microbial Sensitivity Tests MH - Models, Molecular MH - Molecular Sequence Data MH - Nitric Oxide/biosynthesis MH - Phylogeny MH - Protein Conformation MH - Solutions MH - Cathelicidins EDAT- 2013/04/19 06:00 MHDA- 2013/07/10 06:00 CRDT- 2013/04/19 06:00 PHST- 2013/04/19 06:00 [entrez] PHST- 2013/04/19 06:00 [pubmed] PHST- 2013/07/10 06:00 [medline] AID - 10.1021/jm4004158 [doi] PST - ppublish SO - J Med Chem. 2013 May 9;56(9):3546-56. doi: 10.1021/jm4004158. Epub 2013 Apr 29.