When grown from the surface of proteins, negatively charged polymers cause irreversible inactivation, thereby limiting the breadth of the synthetic space that negatively charged protein-polymer conjugates can be applied to. More broadly speaking, independent of polymer and synthetic approach, almost all protein-polymer conjugates are less active than their precursors. After more than a decade without major advances in understanding why the attachment of some polymers so sharply deactivates enzymes, we focused our attention on a technique to protect enzymes from the growth of a deactivating polymer by restoring the charge at the protein surface during polymer attachment. We synthesized an amino-reactive positively charged atom transfer radical polymerization initiator that inserted a permanent positive charge at the site of bio-macroinitiator attachment. Preserving the surface charge through attachment of the permanent positively charged initiator led to the first observation of activity of enzymes that were coupled to negatively charged homopolymers.