Inhibition of Cell Adhesion to Fibronectin by Oligopeptide-Substituted Polynorbornenes

Polynorbornenes substituted with two different peptide sequences from the RGD-containing integrin cell-binding domain of fibronectin are potent inhibitors of human foreskin fibroblast cell adhesion to fibronectin-coated surfaces. Ring-opening metathesis polymerization (ROMP) using Ru═CHPh(Cl)_2(PCy_3)(DHIMes) (1) as an initiator produced polymers substituted with GRGDS and PHSRN peptide sequences. The inhibitory activity was quantified for these polymers and compared to the free peptides and GRGES-containing controls. A homopolymer substituted with GRGDS peptides was significantly more active than the free GRGDS peptide (IC_(50) of 0.18 ± 0.03 and 1.33 ± 0.20 mM respectively), and the copolymer containing both GRGDS and PHSRN is the most potent inhibitor (IC_(50) of 0.04 ± 0.01 mM). These results demonstrate that significant enhancements of observed biological activity can be obtained from polymeric materials containing more than one type of multivalent ligand and that ROMP is a useful method to synthesize such well-defined copolymers