Synthesis of peptide-drug conjugates for controlled release in response to stimuli

Abstract

The aim of this research project is to study the synthesis of a drug-peptide conjugate, in order to achieve a controlled release of the drug in response to stimuli. The peptide has to be synthesized from precursors and achieve a successful peptide formation, looking for an ideal peptide coupling attached with a specific drug. The peptide to synthesize is P-FFLG-OH by a solution phase peptide method, due to the interested small size of the molecule. Deferoxamine (DFOA, Figure 6) is the selected drug to link covalently to the peptide. DFOA is a small and polar molecule that can be isolated as natural product from Streptomyces pilosus. This drug is a chelating agent that is used to treat acute iron poisoning and hemochromatosis, a metabolic and genetic disorder in which the body leads an excess of iron. Moreover, it is a potential novel therapeutic agent to improve healing of chronic wounds, as some studies have demonstrated that DFOA can decrease inflammation, enhanced angiogenesis and wound maturation. More accurately, DFOA could be a potentially heal cutaneous wounds in patients with diabetes.