Antifreeze (glyco)proteins, AF(G)Ps, from polar fish, represent a remarkable group of biomacromolecules which allow extremophiles to survive in freezing temperatures. AF(G)Ps are however unsuited to biomedical translation, and synthetic analogues are needed to mimic their ice recrystallisation inhibitory properties, which may find use in cryopreservation.<br/>Despite the lack of an X-Ray crystal structure of AF(G)P, its adoption of an amphipathic polyproline II like helix is believed to be responsible for its activity. A variety of species which have been found to be IRI active (such as Nisin A) have also been shown to possess these distinct amphipathic regions. We are therefore interested in developing new IRI active biomimetics of AF(G)Ps based on synthetic macromolecular scaffolds, by drawing upon the observations of structural amphipathy in the natural products. We are engaged in the rational design and synthesis of new biomimetic species featuring amphipathic character, followed by IRI activity screening.<br/><br/>Here I will showcase our 2nd generation IRI-active glycopolymers which have been designed to mimic AF(G)Ps. In particular, I will demonstrate how we can use the local hydrophobic/philic balance of the polymers, rather than designed ice-binding motifs, as a universal route to introduce IRI activity. A series of amphipathic monomers polymerised by Ring-opening Metathesis Polymerisation (ROMP) yielded a highly potent panel of IRI active macromolecules. As confirmed by small-angle neutron scattering (SANS), the intrinsic structural rigidity provided for by ROMP (which is unobtainable through classical radical polymerisation methods, and gives rigid-rod like structures), supports a mechanism of activity driven by amphipathy, highlighting the importance of spatial domain segregation in rational IRI design.

Facially amphipathic glycopolymers to mimic the 3-D structure of antifreeze glycoproteins

256th National Meeting (2018)

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