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Research


Bioadhesives

The idea is to make "peptide binding peptides" which complement each other and bind together as a result of pre-organization and hydrogen bonding, inspired by the patterns seen in DNA base pairing. If one peptide is attached to one surface, and its complement is attached to a separate surface, the two surfaces can be joined when the peptides bind. The bonding can be made "permanent" if the amino acid cystine is strategically placed in the sequences, to give a bound entity with a disulfide bond. Note that the "surface" referred to above could be a protein, so this technology could also be a way to attach together different proteins, or even attach proteins to surfaces.
     
Arginine Turn

A serendipitous discovery made while designing small molecule binding peptides, this six amino acid peptide folds well in solution around a central arginine core to bring its amino and carboxy termini close together, which can be easily detected using IMAC chromatography. If the ends of the peptide are elaborated with three amino acid long "arms," the arms are held in close proximity, which imparts interesting binding features to the peptide, including the ability to bind phosphate and hydroxylated aromatics. We are exploring this as well as a two-cysteine mutant which has the ability to control its binding allosterically via formation of a disulfide bond.

Clam Shell

If the Arginine Turn is simply expressed twice in a peptide, with a two-amino acid spacer, the two turns fold separately and arrange themselves with their amino and carboxy ends close together (as in a clam shell), as judged by the GFP-peptide fusion's high IMAC affinity. These clam shells have a deep cleft (that is, the clam's "mouth")  that is a potential binding pocket for ligands.

Clam Shell Binding

The binding observed so far for the Arginine Turn is impressive. The clam shell structure, with its high degree of structure and pre-organization, is envisioned to also have small organic molecule binding capabilities. So far we have seen reasonable binding to certain dyes which opens the possibility of energy transfer from GFP to the dye molecule (FRET).

Note: All these experiments were done quickly and cheaply using the technology developed at Oligometrics, where a host of different designed peptides are attached to GFP using simple molecular biology techniques and analyzed quickly and easily using HIC and IMAC chromatography.