Collagen Mimicry with a Short Collagen Model Peptide

Abstract Mimicking triple helix and fibrillar network of collagen through collagen model peptide(CMP) with short GPO tripeptide repeats is a great challenge. Herein, a minimalistic CMP comprising only five GPO repeats [(GPO) 5 ] is presented. This novel approach involves the fusion of ultrashort peptide with the synergetic power of π‐system and β‐sheet formation to short CMP (GPO) 5 . Accordingly, a hydrogel‐forming, fluorenylmethoxycarbonyl (Fmoc)‐functionalized ultrashort peptide (NFGAIL) is fused at the N‐terminus and phenylalanine at the C‐terminus of (GPO) 5 (Fmoc‐NFGAIL‐(GPO) 5 ‐F‐COOH, FmP‐5GPO). At room temperature, it forms a robust triple helix in aqueous buffer solution and has a relatively high melting point of 35 °C. The fluorenyl motif stabilizes the triple helix by aromatic π–π interactions as in its absence, triple helix is not formed. NFGAIL, which forms a β‐sheet, also aids in triple helix stabilization via intermolecular hydrogen bonding and hydrophobic interactions. FmP‐5GPO forms highly entangled nanofibrils with a micrometer length, which have excellent cell viability. The achievement of stable triple helix and fibrils in such a short CMP(FmP‐5GPO) sequence is a challenging feat, and its significance in CMP‐based biomaterials is undeniable. The present strategy highlights the potential for developing new CMP sequences through intelligent tuning of fusion peptides and GPO repeats.