title: Melittin-glutathione S-transferase fusion protein exhibits anti-inflammatory properties and minimal toxicity.
abstract: Although potent, proteins often require chemical modification for therapeutic use. Immunogenicity, difficult synthesis, and scale-up of these modifications are all engineering obstacles that stand in the way of expanding the use of these therapeutics. Melittin, a peptide derived from bee venom, has been shown to modulate inflammation. Although potentially therapeutic, the native peptide causes cell lysis and toxicity significantly hindering therapeutic application. Based upon the knowledge of the pore formation mechanism, we examined the toxicity and therapeutic effect of a melittin fusion protein with glutathione-S-transferase. The fusion of melittin and glutathione S-transferase results in diminished toxicity of the peptide and retained anti-inflammatory properties at doses that exceed toxic concentration of native melittin. Our results suggest that fusion proteins, particularly those of glutathione-S-transferase, may be facile modifications to control protein activity.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Rayahin
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Buhrman
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois, Chicago, IL 60612-7231, USA; Department of Bioengineering, University of Illinois, Chicago, IL 60607-7052, USA; Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL 60612-4319, USA. Electronic address: rag@uic.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gemeinhart
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001514:Bee Venoms / Q000494:pharmacology; D002478:Cells, Cultured; D005982:Glutathione Transferase / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects; D008555:Melitten / Q000494:pharmacology*; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D001514:Bee Venoms; D010455:Peptides; D011994:Recombinant Proteins; D008555:Melitten; D005982:Glutathione Transferase
keywords: Fusion protein; Glutathione S-transferase; Inflammation; Macrophage; Melittin; Protein therapeutic