Attachment of a chain of poly(ethylene glycol) (PEG) to a therapeutic protein, a 
process widely known as PEGylation, can lead to several beneficial effects. It 
has the potential to significantly delay aggregation of the protein by steric 
shielding, a frequently encountered issue in the development of protein drugs. 
Moreover, it can modify the pharmacokinetic profile of the PEGylated protein by 
delaying renal excretion, leading to a longer half-life (t1/2) of the drug. By 
steric hindrance, it can also inhibit interactions between the protein drug and 
proteases as well as the host immune system, thereby inhibiting inactivation of 
the PEGylated protein and also attenuating its immunogenicity. Unfortunately, 
the effect of steric hindrance also applies to protein drug-target interaction, 
leading to a (partial) loss of efficacy. In order to avoid this undesirable 
effect, several efforts have been made to link PEG to a protein in a noncovalent 
way, providing the protein with several of the beneficial effects of PEGylation 
while also taking advantage of its native affinity to its target.