Abstract
Matrix metalloproteinases (MMPs) play critical roles in the invasiveness of cancerous cells and metastasis of solid tumors. MMP-9 is a member of this protease family, which is extremely overexpressed in metastatic cells. Here, we described a cyclic peptide which inhibits the MMP-9 activity with high potency. This inhibitor selectively binds to the MMP-9 fibronectin domain and interferes with the interaction of gelatinous substrates with MMP-9, thereby suppressing its gelatinolytic activity. Previously, we isolated and developed a linear peptide, named as RSH-12, from a phage display library which displayed promising results in the inhibition of MMP-9. Next, we decided to improve its biostability via cyclization chemistry and show that RSH-12 has a considerably enhanced stability in human serum. Moreover, the cyclic peptide is still associated with a high potency to inhibit the invasion activity of a human fibrosarcoma cell line. These results demonstrate that the designed cyclic peptide might be considered as a promising therapeutic moiety to target the MMP-9 for the treatment of cancer.
NSTL