Linker peptide joins drugs to devices

The team, from the University of Texas at Austin, have accomplished the feat by identifying a peptide that attaches to polypyrrole, a synthetic polymer that has promise as a new biomaterial for medical devices.

The researchers screened a billion candidates to find the molecule-binding peptide, called T59, and also developed a modification of it that can be used to bind cells.

Christine Schmidt, who led the research team, said: "It will be very useful from a biomedical standpoint to be able to link factors to polypyrrole in the future that stimulate nerve growth or serve other functions."​ The work is published online in the journal Nature Materials​.

Polypyrrole is of interest for tissue engineering and other purposes because it is a non-toxic plastic that conducts electricity. Researchers in Schmidt's laboratory have been investigating the material's ability to help severed nerve branches (neurites) regenerate.

If the severed neurites are wrapped in the polymer, the application of an electric field has been shown to enhance neurite repair. Now, the ability to attach proteins to polypyrrole means that growth-enhancing factors could also be linked to this plastic wrapping, further stimulating neurite regeneration. In time, the hope is that the technique could be scaled up to allow the repair of bigger nerves.The screening process involved the generation of peptides that were displayed on the outer surface of a harmless carrier virus called a bacteriophage.To hunt for the plastic-preferring peptide, the researchers added a solution containing the bacteriophages to a container lined with polypyrrole. The bacteriophages that didn't wash away were retested on a new polypyrrole-coated container, a process that was repeated four more times.

T59 was selected as the best binding peptide, a property helped by the inclusion of aspartic acid in the molecule. This amino acid carries a negative charge, which in T59 appeared to be drawn to the positively charged surface of the polypyrrole the way magnets of opposite charges cling together. Yet other peptides containing aspartic acid didn't attach to polypyrrole, leading the researchers to speculate that something contributed by the other amino acids in T59 influenced its 3-dimensional shape in a way that augmented its plastic preference.

Schmidt's laboratory intends to study T59 as a linker to other molecules in the future, possibly including vascular endothelial growth factor, which stimulates the growth of new blood vessels, in the hope of developing materials that could be used to treat cardiovascular diseases.

In addition, they will use the bacteriophage analysis approach, called high-throughput combinatorial screening, to look for peptide linkers for other plastics such as polyglycolic acid under study for tissue-repair or tissue-engineering purposes.

"This is a powerful technique that can be used for biomaterials modification,"​ Schmidt said. "It hasn't really been explored very much until now."​