title: Deletion of two C-terminal Gln residues of 12-26-residue fragment of melittin improves its antimicrobial activity.
abstract: In our previous paper it was shown that the two C-terminal Gln residues of a C-terminal 15-residue fragment, Mel(12-26) (GLPALISWIKRKRQQ-NH2), of melittin and a series of individual substituted analogues might not involved in the interaction with bacterial membranes. In this paper, peptides with one and two Gln residues deletion, respectively, Mel(12-25) and Mel(12-24), were synthesized and characterized. Both of the deletion peptides showed higher antimicrobial activities than the parent peptide, Mel(12-26). If both of the Gln residues of Mel(12-26) were respectively replaced by a hydrophilic amino acid Gly, the antimicrobial activity increased slightly. If the Gln residue of Mel(12-25) was replaced by a hydrophobic amino acid Leu, the antimicrobial activity changed little, although the substituted peptide possessed much higher hydrophobicity and higher alpha-helical conformation percentage in 1,1,1,3,3,3-hexafluoro-2-propanol/water determined by circular dichroism spectroscopy (CD) than the parent peptide. These results indicated that the two C-terminal residues might be indeed not involved in the binding to bacterial membranes. The antimicrobial activity increasing with the residue deletion may be caused by the decrease of the translational and rotational entropic cost of the binding of the peptides to bacterial membranes because of the lower molecular weights of the deletion peptides.
authors.affiliation: Institute of Polymer Chemistry, State Key Laboratory of Function Polymer Materials for Adsorption and Separation, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.forename: Suxia
authors.initials: S
authors.lastname: Chen
authors.forename: Shunzi
authors.initials: S
authors.lastname: Li
authors.forename: Husheng
authors.initials: H
authors.lastname: Yan
authors.forename: Yunge
authors.initials: Y
authors.lastname: Fan
authors.forename: Huaifeng
authors.initials: H
authors.lastname: Mi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001514:Bee Venoms; D001516:Bees; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D005973:Glutamine / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008555:Melitten / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000737:chemistry; D020005:Propanols / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014364:Tryptophan / Q000737:chemistry; D014867:Water / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001514:Bee Venoms; D005973:Glutamine; D008055:Lipids; D008555:Melitten; D010455:Peptides; D020005:Propanols; D014364:Tryptophan; D014867:Water; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated