Peptides and Proteins As Drugs

Relatively small modifications of clinically useful endogenous compounds have been shown to have therapeutically beneficial effects on their pharmacodynamic and pharmacokinetic properties. These effects include increased potency and effect selectivity, and prolonged duration of action. In addition, these modifications have resulted in compounds that can be administered orally where only parenteral administration was previously possible. One type of modification resulting in distinctive properties is exemplified by the hybrid interferons produced by the recombination of segments of genes coding for different molecular species. Chemical modification has also resulted in many examples of analogs of natural peptides that are more potent, more selective and more stable than the endogenous compounds. Conjugation to peptide or protein carriers is a third method used to selectively modify the properties of an endogenous compound. The carriers that have been used include synthetic polypeptides, endogenous proteins, toxins and monoclonal antibodies. The effect that covalent attachment to a carrier has on the properties of a ligand is highly dependent upon the carrier, the ligand and the linkage between them.