Polymer-enhanced biomacromolecules

Protein-polymer conjugates are complex molecules with major societal implications. Many advances in the fields of medicine, biotechnology and nanotechnology have been associated with the development of these bioconjugates. Synthetic polymers are usually attached to proteins in order to change or enhance their native properties. Polymer-enhanced biomacromolecular activity, specificity and stability are of particular interest. The most visible impact of coupling polymers to proteins has been on therapeutic proteins. There is a rich history and literature which describes how such polymers increase protein lifetimes in vivo and mask the protein from circulating antibodies and immune cells. Although the attachment of polymers to therapeutic proteins has these benefits, it often comes at an unpredictable cost of reduced functionality. Several studies have shown modification decreases the bioactivity of therapeutic proteins. In this review, we explore different synthetic approaches to protein-polymer conjugation and whether more rational and controlled attachment chemistries can reveal how to create molecular sieves around a protein without sacrificing activity. Research has begun to reveal the influence of polymer molar mass, number of attached polymers, synthetic approach, and polymer architecture on molecular sieving properties. Although rational approaches to polymer-based protein engineering are relatively new additions to the arsenal of approaches to the design of protein-displayed molecular sieves, general trends are emerging that will help guide future research in the field.