Suppression of neovascularization and experimental arthritis by D-form of anti-flt-1 peptide conjugated with mini-PEG((TM))
SCIE
SCOPUS
- Title
- Suppression of neovascularization and experimental arthritis by D-form of anti-flt-1 peptide conjugated with mini-PEG((TM))
- Authors
- Kong, JS; Yoo, SA; Kang, JH; Ko, W; Jeon, S; Chae, CB; Cho, CS; Kim, WU
- Date Issued
- 2011-12
- Publisher
- SPRINGER
- Abstract
- Extensive angiogenesis in the synoviums is a characteristic pathology of rheumatoid arthritis (RA). We have demonstrated that anti-flt-1 hexapeptide, GNQWFI, specifically inhibits the interaction of VEGF or PlGF with its receptor flt-1 (Yoo et al. [13]). In this study, we investigate the feasibility of the synthetic D-form of anti-flt-1 hexapeptide conjugated with 8-amino-3,6-dioxaoctanoic acid (mini-PEG((TM))) for treatment of RA. We first modified the structure of anti-flt-1 peptide from the L-form (GNQWFI) to all D-form (gnqwfi; allD) and then conjugated allD with mini-PEG((TM)) to enhance its stability. The result showed that the allD anti-flt-1 peptide showed an increased stability in the sera without major loss of inhibitory activity. The allD and its mini-PEGylated derivative similarly suppressed wounding migration, chemotaxis, and tube formation of endothelial cells in vitro. However, in the Matrigels assay, the in vivo anti-angiogenic activity of mini-PEGylated allD was stronger than that of native allD or L-form. Moreover, oral and subcutaneous administration of mini-PEGylated allD, but not oral feeding of original L-form, successfully suppressed severity of collagen-induced arthritis. After a single subcutaneous injection, the Cy5-labeled mini-PEGylated allD was found to be distributed systemically and accumulated in arthritic joints of mice, particularly in joints with a severe clinical score. In conclusion, our data suggests that mini-PEGylated allD is more beneficial in the treatment of RA than unmodified anti-flt-1 peptides, since it has increased stability and the possibility of oral delivery, and could be applied to treat angiogenesis-dependent human diseases, including RA.
- Keywords
- VEGF; Anti-flt-1 peptide; D-form; Mini-PEG; Angiogenesis; Chronic arthritis; COLLAGEN-INDUCED ARTHRITIS; GROWTH-FACTOR; RHEUMATOID-ARTHRITIS; INTESTINAL PERMEABILITY; POLYETHYLENE-GLYCOL; ORAL DELIVERY; TUMOR-GROWTH; ANGIOGENESIS; VEGF; BEVACIZUMAB
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17040
- DOI
- 10.1007/S10456-011-9226-0
- ISSN
- 0969-6970
- Article Type
- Article
- Citation
- ANGIOGENESIS, vol. 14, no. 4, page. 431 - 442, 2011-12
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