An unusual covalent binding of hydroxysuccinimidyl ester activated polyethylene glycol), PEG, was found in the modification of a genetic variant of mouse epidermal growth factor (EGF): PEG was bound not only to the amino groups of the polypeptide as expected, but to a tyrosine residue as well. This unexpected PEGylation is related to the tyrosine environment in the peptide which does not occur in human EGF; furthermore, it is related to PEG size since it was found to occur to a greater extent with the PEG 5,000 molecular weight, than with the more hindered PEG 10,000.
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