Bioconjugation of polymers to proteins is a method to
impart improved
stability and pharmacokinetic properties to biologic systems. However,
the precise effects of polymer architecture on the resulting bioconjugates
are not well understood. Particularly, cyclic polymers are known to
possess unique features such as a decreased hydrodynamic radius when
compared to their linear counterparts of the same molecular weight,
but have not yet been studied. Here, we report the first bioconjugation
of a cyclic polymer, poly(ethylene glycol) (PEG), to a model protein,
T4 lysozyme, containing a single engineered cysteine residue (V131C).
We compare the stability and activity of this conjugate with those
of a linear PEG-T4 lysozyme analogue of similar molecular weight.
Furthermore, we used molecular dynamics (MD) simulations to determine
the behavior of the polymer–protein conjugates in solution.
We introduce cyclic polymer–protein conjugates as potential
candidates for the improvement of biologic therapeutics.