title: Functional peptide-polyurethane conjugates with extended circulatory half-lives.
abstract: Peptides containing the RGD sequence were covalently attached to an isocyanate-containing polyurethane prepolymer and the biological properties of the complexes were evaluated. For the pentapeptide H2N-Tyr-Arg-Gly-Asp-Ser-OH (single-letter code, YRGDS), polymer conjugation lead to an increased half-life in the blood circulation of mice to > 10 h. The effect of covalent attachment of polymer on biological activity was examined in a related peptide, H2N-Gly-Arg-Gly-Asp-Ser-Pro-Ala-Cys- OH (GRGDSPAC). Inhibition of B16-F10 melanoma cell attachment and spreading on plates coated with fibronectin by an RGD-containing peptide and polymer-conjugated GRGDSPAC was observed to occur at similar concentrations. We conclude that the conjugation of peptides containing the Arg-Gly-Asp motif to this polymer resolves previous problems of their rapid loss from the circulation, while still allowing retention of full biological inhibitory activity.
authors.affiliation: W. R. Grace & Company-Conn., Department of Mammalian Cell Research, Columbia, Maryland 21044.
authors.forename: J A
authors.initials: JA
authors.lastname: Braatz
authors.forename: Y
authors.initials: Y
authors.lastname: Yasuda
authors.forename: K
authors.initials: K
authors.lastname: Olden
authors.forename: K M
authors.initials: KM
authors.lastname: Yamada
authors.forename: A H
authors.initials: AH
authors.lastname: Heifetz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007457:Iodine Radioisotopes; D017953:Isocyanates / Q000737:chemistry; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D011140:Polyurethanes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D007457:Iodine Radioisotopes; D017953:Isocyanates; D010455:Peptides; D011140:Polyurethanes