Methods for synthesizing proinsulin polypeptides are described that include
a contacting a proinsulin polypeptide including an insulin polypeptide coupled
to one or more peptides by peptide bond(s) capable of being cleaved to yield the
insulin polypeptide with an oligomer under conditions sufficient to couple the
oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide
a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides
from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer
conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are
also described as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing
C-peptide polypeptide-oligomer conjugates are also described.