Open AccessModification of a novel angiogenic peptide, AG30, for the development of novel therapeutic agents
Author(s) -
Nakagami Hironori,
Nishikawa Tomoyuki,
Tamura Nao,
Maeda Akito,
Hibino Hajime,
Mochizuki Masayoshi,
Shimosato Takashi,
Moriya Toshinori,
Morishita Ryuichi,
Tamai Katsuto,
Tomono Kazunori,
Kaneda Yasufumi
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01406.x
Subject(s) - peptide , angiogenesis , chemistry , pharmacology , cancer research , computational biology , medicine , biology , biochemistry
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.