Receptor Mimicking Tgf-Beta 1 Binding Peptide For Targeting Tgf-Beta 1 Signaling

Prolonged and elevated transforming growth factor-beta 1 (TGF-beta 1) signaling can lead to undesired scar formation during tissue repair and fibrosis that is often a result of chronic inflammation in the lung, kidney, liver, heart, skin, and joints. We report new TGF-beta 1 binding peptides that interfere with TGF-beta 1 binding to its cognate receptors and thus attenuate its biological activity. We identified TGF-beta 1 binding peptides from the TGF-beta 1 binding domains of TGF-beta receptors and engineered their sequences to facilitate chemical conjugation to biomaterials using molecular docking simulations. The in vitro binding studies and cell-based assays showed that RIP Delta, which was derived from TGF-beta type I receptor, bound TGF-beta 1 in a sequence-specific manner and reduced the biological activity of TGF-beta 1 when the peptide was presented either in soluble form or conjugated to a commonly used synthetic biomaterial. This approach may have implications for clinical applications such as treatment of various fibrotic diseases and soft tissue repair and offer a design strategy for peptide antibodies based on the biomimicry of ligand-receptor interactions.