Covalent conjugation of water-soluble polymers to proteins is critical for evading the immune surveillance in the field of biopharmaceuticals. The most common and long-standing polymer modification is the attachment of polyethylene glycol (PEG), termed PEGylation, which has led to several clinically approved pharmaceuticals. Recent data indicates that brush-type polymers significantly enhance in vitro and in vivo properties. Herein, the polymer conformation of polyethylene glycol is detailed and compared to water-soluble polyacrylates and polynorbornenes when attached to icosahedral viral nanoparticles. Small-angle neutron scattering reveals vastly different polymer conformations between the multivalent conjugates. PEG shows an extended random coil conformation, exhibiting minimal interaction with the capsid. In contrast, acrylate and norbornene polymers strongly interact with the capsid, forming a raspberry like shell on the capsid surface. Cryo-electron microscopy reconstruction of polynorbornene conjugates showed that the polymer associates with the outer surface of the viral capsid and forms a heterogeneous halo extending ~15 nm from the viral surface. Finally, the immune recognition of conjugated particles was evaluated. These findings provide structural insight into the conformations of multivalent polymer conjugates and will likely impact the future design of new polymer conjugates in the pharmaceutical field.

Polymer structure and conformation alters immune recognition of viral nanoparticle-polymer conjugates

253rd National Meeting (2017)

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