title: Modification of a novel angiogenic peptide, AG30, for the development of novel therapeutic agents.
abstract: We previously identified a novel angiogenic peptide, AG30, with antibacterial effects that could serve as a foundation molecule for the design of wound-healing drugs. Toward clinical application, in this study we have developed a modified version of the AG30 peptide characterized by improved antibacterial and angiogenic action, thus establishing a lead compound for a feasibility study. Because AG30 has an α-helix structure with a number of hydrophobic and cationic amino acids, we designed a modified AG30 peptide by replacing several of the amino acids. The replacement of cationic amino acids (yielding a new molecule, AG30/5C), but not hydrophobic amino acids, increased both the angiogenic and the antimicrobial properties of the peptide. AG30/5C was also effective against methicillin-resistant Staphylococcus aureus (MRSA) and antibiotic-resistant Pseudomonas aeruginosa. In a diabetic mouse wound-healing model, the topical application of AG30/5C accelerated wound healing with increased angiogenesis and attenuated MRSA infection. To facilitate the eventual clinical investigation/application of these compounds, we developed a large-scale procedure for the synthesis of AG30/5C that employed the conventional solution method and met Good Manufacturing Practice guidelines. In the evaluation of stability of this peptide in saline solution, RP-HPLC analysis revealed that AG30/5C was fairly stable under 5°C for 12 months. Therefore, we propose the use of AG30/5C as a wound-healing drug with antibacterial and angiogenic actions.
authors.affiliation: Division of Gene Therapy Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. nakagami@gts.med.osaka-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Nao
authors.initials: N
authors.lastname: Tamura
authors.forename: Akito
authors.initials: A
authors.lastname: Maeda
authors.forename: Hajime
authors.initials: H
authors.lastname: Hibino
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimosato
authors.forename: Toshinori
authors.initials: T
authors.lastname: Moriya
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tamai
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tomono
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
mesh_terms: D042501:Angiogenic Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002942:Circular Dichroism; D015195:Drug Design; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D014945:Wound Healing / Q000187:drug effects
chemical_list: C576452:AG30 peptide; C576453:AG30-5C peptide; D042501:Angiogenic Proteins; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides