Novel peptide design and evaluation against actin and α5β1integrin

Abstract Adhesion-dependent cells rely on actin and α5β1 integrin interactions to establish the cytoskeleton, signaling their survival and growth. We investigated the persistence of the complex in early transformed rat fibroblast cells, which opens the possibility of halting tumor growth by inhibiting the formation of the actin and α5β1 integrin complex. Hence, actin and α5β1 integrin were targeted for developing novel peptides to disrupt their association and inhibit tumor growth. Seventeen heptapeptides were designed based on actin- α5β1 integrin complex by using in silico techniques such as peptide designing, homology modeling, docking, molecular dynamics simulations, and in vitro methods using a cellular tumor model system to study their viability using MTT assay. Docking was performed for actin, α5β1 integrin with existing peptide inhibitor ATN 161, designed peptides and small molecule inhibitor Cytochalasin D using Schrodinger. Docking revealed that actin and α5β1 integrin had higher affinity for sixteen and five peptides respectively. TRFKKGY, the top ranked peptide of actin and α5β1 integrin was cytotoxic to transformed rat fibroblast cells grown in non-adherent conditions. This data suggests that the peptide designed has a minimal inhibitory effect on cell growth. However, it showed maximum cell death in transformed rat fibroblast F111 cells.