Title
Targeted and MMP-2/9 responsive peptides for the treatment of rheumatoid arthritis
Author
Na Li, Yonghui Qiao, Lingping Xue, Shiqi Xu, Nan Zhang
Year
2019
Journal
International Journal of Pharmaceutics
Abstract
Bioactive peptides are attractive candidates for drug development. QAW is a tripeptide that is obtained from an anti-inflammatory protein-Annexin A1 (ANXA1). Previous studies showed that QAW alleviated inflammation in experimental colitis and inflammatory bowel disease via NF-κB inhibition. This study establishes adjuvant-induced arthritis (AIA) mouse models and explores the anti-inflammatory efficacy of QAW in AIA mice. To enhance the targeting, responsiveness, and efficacy of QAW to inflammation, QAW (Q) is modified with a cell penetrating peptide (T), a matrix metalloproteases-2/9 (MMP-2/9) digestive peptide (M), and an inflammation targeting peptide-RGD (R). The designed RMTQ demonstrates enhanced delivery to cytoplasm, higher reduction of pro-inflammatory factors, and better efficacy than QAW. The anti-inflammatory efficacy of RMTQ is similar to that of DEX in this study whereas RMTQ treatment shows a higher safety than that of DEX. In sum, this study demonstrates that RMTQ can be a potential therapeutic for inflammatory arthritis.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Biochemistry, Pharmaceutical