Application

B10 protein polymers can be used to build small diameter arterial vascular grafts as well as a host of other potential cardiovascular constructs. The proteins may provide an important vehicle for the design of a variety of medically implanted devices.

Technical Summary

The emergence of genetically engineered synthetic polypeptides has enabled the design of protein polymers composed of complex peptide sequences in which individual peptide repeat sequences can be selected with distinct mechanical, chemical, or biological properties. The inventors recently synthesized a new class of protein block copolymers that are derived from elastin-mimetic polypeptide sequences in which identical endblocks of a hydrophobic, plastic-like sequence are separated by a central hydrophilic, elastomeric block. Specifically, elastin-mimetic polypeptides depend critically on the identity of the residues within the pentapeptide repeat sequence [(Val/Ile)-Pro-Xaa-Yaa-Gly]. Alterations in the identity of the fourth residue (Yaa) modulates the position of the inverse temperature transition (Tt) of the polypeptide in aqueous solution in a manner commensurate with the effect of the polarity of the amino acid side chain on polymer-solvent interactions. For example, increasing the polarity of this residue raises the temperature at which the protein coacervates. Significantly, a substitution in the third (Xaa) position of the repeat sequence from the consensus glycine residue to alanine changes the mechanical response of the material from elastic to plastic deformation. The triblock protein copolymer has the potential to act as a two-phase network when hydrated, in that the hydrophilic block remains conformationally flexible and elastomeric, while the hydrophobic block forms physical or virtual cross-links through hydrophobic aggregation.

Physically cross-linked protein-based materials possess a number of advantages over their chemically cross-linked counterparts, including ease of processing and the ability to avoid the addition or removal of chemical reagents or unreacted intermediates. Prior studies suggest that the density and strength of the physical cross-links are important determinants of both mechanical responses and long-term material stability of two-phase protein networks. Therefore, to enhance the mechanical behavior of these materials, a new elastin-mimetic triblock copolymer, designated B10, was synthesized, which contains hydrophobic endblocks that are nearly twice as large as the prior versions of this triblock protein polymer.

Developmental Stage

B10 polymers have been synthesized and tested.