Amino acids and peptides. Part 39: A bivalent poly(ethylene glycol) hybridcontaining an active site (RGD) and its synergistic site (PHSRN) of fibronectin

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, indicatin g that a spatial array between RGD and PHSRN in fibronectin may be necessar y for synergic activity. Here, we have used an amino acid type poly(ethylen e 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 aaP EG-RGD promoted cell spreading activity, PHSRN-aaPEG had no activity. The P HSRN-aaPEG-RGD hybrid strongly promoted cell spreading compared with aaPEG- RGD. These results suggest that the PHSRN sequence in the PHSRN-aaPEG-RGD m olecule synergistically enhances the cell spreading activity of the RGD seq uence, and that the bivalent aaPEG hybrid method may be useful for conjugat ing functionally active peptides. (C) 2001 Elsevier Science Ltd. All rights reserved.