Open AccessDevelopment of a novel antimicrobial peptide, AG‐30, with angiogenic properties
Author(s) -
Nishikawa Tomoyuki,
Nakagami Hironori,
Maeda Akito,
Morishita Ryuichi,
Miyazaki Nobuhiko,
Ogawa Toshihiro,
Tabata Yasuhiko,
Kikuchi Yasushi,
Hayashi Hiroki,
Tatsu Yoshiro,
Yumoto Noboru,
Tamai Katsuto,
Tomono Kazunori,
Kaneda Yasufumi
Publication year - 2009
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.1582-4934.2008.00341.x
Subject(s) - antimicrobial , peptide , angiogenesis , computational biology , cancer research , chemistry , microbiology and biotechnology , medicine , biology , biochemistry
The utility of various synthetic peptides has been investigated in clinical trials of the treatment of cancers, infectious diseases and endocrine diseases. In the process of functional gene screening with in silico analysis for molecules with angiogenic properties, we generated a small peptide, angiogenic peptide (AG)‐30, that possesses both antimicrobial and pro‐inflammatory activities. AG‐30 has an α‐helix structure with a number of hydrophobic or net positively charged amino acids and a propensity to fold into amphipathic structures. Indeed, AG‐30 exhibited antimicrobial activity against various bacteria, induced vascular endothelial cell growth and tube formation in a dose‐dependent manner and increased neovascularization in a Matrigel plug assay. As a result, AG‐30 up‐regulated expression of angiogenesis‐related cytokines and growth factors for up to 72 hrs in human aortic endothelial cells. To further evaluate the angiogenic effect of AG‐30 in vivo , we developed a slow‐release AG‐30 system utilizing biodegradable gelatin microspheres. In the ischaemic mouse hind limb, slow‐release AG‐30 treatment results in an increase in angiogenic score, an increase in blood flow (as demonstrated by laser Doppler imaging) and an increase in capillary density (as demonstrated by immunostaining with anti‐CD31 antibody). These data suggest that the novel peptide, AG‐30, may have therapeutic potential for ischaemic diseases.