title: Inhibition of cell adhesion to fibronectin by oligopeptide-substituted polynorbornenes.
abstract: 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.
authors.affiliation: Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: H D
authors.initials: HD
authors.lastname: Maynard
authors.forename: S Y
authors.initials: SY
authors.lastname: Okada
authors.forename: R H
authors.initials: RH
authors.lastname: Grubbs
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009842:Oligopeptides / Q000494:pharmacology*; D010969:Plastics / Q000494:pharmacology*; D011108:Polymers
chemical_list: D005353:Fibronectins; D009842:Oligopeptides; D010969:Plastics; D011108:Polymers; C071464:polynorbornen