The solutions presented herein provide many options to help one decide how to PEGylate a given peptide most effectively. However,
there are three factors that must be taken into account because they can affect the efficiency of PEGylation: the number of
chains attached to a peptide; the molecular weight and structure of the PEG chains; and the attachment site of PEG.
In recent work (11), a synthetic peptide inhibiting the binding of human neonatal Fc receptor to immunoglobulin was PEGylated
in a number of different ways. In vitro and in vivo activity was then compared to determine which method was the most effective. Three different amino acids were either replaced
with lysine, or a C-terminal amine was generated, or a linker amine was generated. The PEGylated peptides were more active
in mice compared with the nonPEGylated version, but only when linked through a specific linker. The linear version was more
active compared with the branched version. Because technology now exists to make different versions, a few should be tested
for each specific peptide.
As PEGylation becomes more well used, such comparative studies may help optimize future PEGylation strategies. Additionally,
as more peptides become drug candidates, testing different ways of linking them to PEG may become a routine part of fine-tuning
them for their final clinical manifestations.
Baosheng Liu is vice-president of research and manufacturing at the American Peptide Company, 777 E. Evelyn Avenue, Sunnyvale, CA 94086.
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