Polyethylene glycol (PEG)-conjugated proteins belong to a new class of biom
olecules that are neither proteins nor polymers, but which are hybrids of t
he two. PEG conjugation of biopharmaceuticals is now common practice in eff
orts to achieve sustained clinical response. However, very little is known
about the strategies and criteria used to produce a well-characterized pegy
lated biomolecule. In this review, the issues of pegylation reagent selecti
on, reaction conditions, process considerations and purification will be ad
dressed, as well as biochemical and biological characterizations. The isola
tion of positional isomers and the determination of pegylation sites will a
lso be included.