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Related Experiment Videos

Functional peptide-polyurethane conjugates with extended circulatory half-lives

J A Braatz1, Y Yasuda, K Olden

  • 1W. R. Grace & Company-Conn., Department of Mammalian Cell Research, Columbia, Maryland 21044.

Bioconjugate Chemistry
|July 1, 1993
PubMed
Summary

Attaching Arg-Gly-Asp (RGD) peptides to a polyurethane polymer significantly increased their circulation half-life in mice. This RGD-polymer conjugate maintained full biological activity, inhibiting melanoma cell attachment.

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Cell Biology

Background:

  • Peptides with the Arg-Gly-Asp (RGD) motif are crucial for cell adhesion.
  • Rapid clearance of RGD peptides from circulation limits their therapeutic potential.
  • Polyurethane prepolymers offer a versatile platform for biomolecule conjugation.

Purpose of the Study:

  • To covalently attach RGD-containing peptides to a polyurethane prepolymer.
  • To evaluate the impact of polymer conjugation on peptide pharmacokinetics.
  • To assess the retention of biological activity in RGD-polymer conjugates.

Main Methods:

  • Covalent attachment of pentapeptide (YRGDS) and hexapeptide (GRGDSPAC) to isocyanate-containing polyurethane.
  • In vivo pharmacokinetic studies in mice to determine circulation half-life.

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  • In vitro cell-based assays to measure inhibition of B16-F10 melanoma cell attachment and spreading on fibronectin-coated plates.

    • Main Results:

    • Polymer conjugation increased the half-life of the pentapeptide (YRGDS) in mouse circulation to over 10 hours.
    • The polymer-conjugated GRGDSPAC peptide demonstrated similar inhibitory concentrations for B16-F10 melanoma cell attachment and spreading compared to the unconjugated peptide.
    • Biological activity, specifically the inhibition of cell adhesion and spreading, was fully retained after polymer conjugation.

    Conclusions:

    • Conjugation of RGD-containing peptides to polyurethane prepolymers effectively overcomes rapid circulation clearance.
    • The RGD-polymer conjugates maintain significant biological inhibitory activity.
    • This approach offers a promising strategy for developing RGD-based therapeutics with improved pharmacokinetic profiles.