Techniques: Chemically-linked knottin dimers with enhanced integrin receptor inhibition
Dimers of the peptide knottin could be used to develop high-affinity integrin receptor inhibitors to treat cancer. Cysteine knottin miniproteins were functionalized with a non-natural amino acid that enabled chemical cross-linking with a dialdehyde-containing crosslinker to enhance integrin receptor-binding. In two cancer cell lines, the knottin dimers showed increased binding affinity for integrin receptors compared with knottin monomers or cilengitide, an integrin receptor-inhibiting peptidomimetic. In human osteosarcoma and breast cancer cell lines, knottin dimers induced more potent inhibition of cell migration and proliferation than knottin monomers or cilengitide. Next steps could include investigating the knottin dimers in an in vivo tumor model...