title: Antimicrobial and anti-inflammatory activities of three chensinin-1 peptides containing mutation of glycine and histidine residues.
abstract: The natural peptide chensinin-1 doesnot exhibit its desired biological properties. In this study, the mutant MC1-1 was designed by replacing Gly in the chensinin-1 sequence with Trp. Mutants MC1-2 and MC1-3 were designed based on the MC1-1 sequence to investigate the specific role of His residues. The mutated peptides presented α-helicity in a membrane-mimetic environment and exhibited broad-spectrum antimicrobial activities; in contrast to Trp residues, His residues were dispensable for interacting with the cell membrane. The interactions between the mutant peptides and lipopolysaccharide (LPS) facilitated the ingestion of peptides by Gram-negative bacteria. The binding affinities of the peptides were similar, at approximately 10 μM, but ΔH for MC1-2 was -7.3 kcal.mol-1, which was 6-9 folds higher than those of MC1-1 and MC1-3, probably due to the conformational changes. All mutant peptides demonstrated the ability to inhibit LPS-induced tumour-necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release from murine RAW264.7 cells. In addition, the representative peptide MC1-1showed better inhibition of serum TNF-α and IL-6 levels compared to polymyxin B (PMB), a potent binder and neutralizer of LPS as positive control in LPS-challenged mice model. These data suggest that the mutant peptides could be promising molecules for development as chensinin-based therapeutic agents against sepsis.
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.|Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China.|State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China.
authors.forename: Weibing
authors.initials: W
authors.lastname: Dong
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Mao
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Kang
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian 116081, China.|Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China.
authors.forename: Dejing
authors.initials: D
authors.lastname: Shang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D006090:Gram-Negative Bacteria / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D000072756:Protein Conformation, alpha-Helical; D000067996:RAW 264.7 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D015850:Interleukin-6; D050505:Mutant Proteins; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C000600263:chensinin-1b