Functional peptide-polyurethane conjugates with extended circulatory half-lives.

J A Braatz; Y Yasuda; K Olden; K M Yamada; A H Heifetz

doi:10.1021/bc00022a003

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Functional peptide-polyurethane conjugates with extended circulatory half-lives.

J A Braatz·Y Yasuda·K Olden·K M Yamada·A H Heifetz

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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.

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Amino Acid Sequence Animals Cell Adhesion Chromatography, High Pressure Liquid Half-Life Iodine Radioisotopes Isocyanates Melanoma, Experimental Mice Mice, Inbred C57BL Molecular Sequence Data Peptides Polyurethanes Tumor Cells, Cultured Journal Article

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J A Braatz, Y Yasuda, K Olden, K M Yamada, A H Heifetz. Functional peptide-polyurethane conjugates with extended circulatory half-lives.. https://doi.org/10.1021/bc00022a003

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