Abstract
Fibronectin contains the active sequence Arg-Gly-Asp (RGD), along with its synergic site Pro-His-Ser-Arg-Asn (PHSRN). However, the PHSRN peptide does not show synergic activity when it is mixed with the RGD peptide, indicating that a spatial array between RGD and PHSRN in fibronectin may be necessary for synergic activity. Here, we have used an amino acid type poly(ethylene glycol) derivative (aaPEG) to design a bivalent PEG hybrid of fibronectin active peptides. We prepared the aaPEG hybrid peptides PHSRN–aaPEG, aaPEG–RGD, and PHSRN–aaPEG–RGD, and tested their biological activity. Whereas aaPEG–RGD promoted cell spreading activity, PHSRN–aaPEG had no activity. The PHSRN–aaPEG–RGD hybrid strongly promoted cell spreading compared with aaPEG–RGD. These results suggest that the PHSRN sequence in the PHSRN–aaPEG–RGD molecule synergistically enhances the cell spreading activity of the RGD sequence, and that the bivalent aaPEG hybrid method may be useful for conjugating functionally active peptides.
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