Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components

A method of synthesizing a modified therapeutic peptide capable of forming a peptidase-stabilized therapeutic peptide conjugate, the peptide comprising between 3 and 50 amino acids and having a carboxy terminal amino acid, an amino terminal amino acid, the method of comprising the steps of:

• a) synthesizing the peptide from the carboxy terminal amino acid or the amino terminal amino acid,
• b) sequentially and selectively oxidizing any pairs of cysteine residues in said therapeutic peptide to form disulfide bridges in said therapeutic peptide;
• c) attaching a protecting group to any remaining cysteine residues that do not form said disulfide bridges in said therapeutic peptide;
• and
• d) coupling a reactive group to the carboxy terminal amino acid, to the amino terminal amino acid, or to an amino acid between the carboxy terminal amino acid and the amino terminal amino acid, wherein the reactive group is capable of reacting with an amino group, an hydroxyl group or a thiol group on blood component to form a covalent bond therewith.