Targeting CD13 with Asn-Gly-Arg (NGR) Peptide-Drug Conjugates

CD13/aminopeptidase N is a multifunctional cell surface metalloprotease expressed in myeloid and activated endothelial cells; in epithelial cells of the intestine, liver, and kidney; and in other cells. A growing body of evidence suggests that CD13 has an important role in inflammation and angiogenesis. Furthermore, a CD13 form selectively expressed by the angiogenic endothelium, but not in normal vessels, is recognized by peptides containing the Asn-Gly-Arg (NGR) motif. Because of this property, NGR peptides have been exploited as ligands for the selective delivery of a variety of therapeutic and imaging agents to angiogenic vessels. In this chapter, we discuss the structural and functional properties of NGR peptides and their potential applications as drug delivery systems in diseases with angiogenesis and inflammatory components. In addition, we discuss the experimental evidence suggesting that the asparagine residue of NGR can rapidly undergo deamidation, a spontaneous reaction that changes NGR to isoDGR (an integrin-binding motif), and the potential biological, pharmacological, and toxicological implications of this sequence transition in peptide-drug conjugates.