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Blood. 2008 Oct 1;112(7):2628-35. doi: 10.1182/blood-2008-04-150862. Epub 2008 Jun 23.

The neovasculature homing motif NGR: more than meets the eye.

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  • 1DIBIT-Department of Oncology and IIT Network Research Unit of Molecular Neuroscience, San Raffaele Scientific Institute, Milan, Italy.


A growing body of evidence suggests that peptides containing the Asn-Gly-Arg (NGR) motif can selectively recognize tumor neovasculature and can be used, therefore, for ligand-directed targeted delivery of various drugs and particles to tumors or to other tissues with an angiogenesis component. The neovasculature binding properties of these peptides rely on the interaction with an endothelium-associated form of aminopeptidase N (CD13), an enzyme that has been implicated in angiogenesis and tumor growth. Recent studies have shown that NGR can rapidly convert to isoaspartate-glycine-arginine (isoDGR) by asparagine deamidation, generating alpha(v)beta(3) ligands capable of affecting endothelial cell functions and tumor growth. This review focuses on structural and functional properties of the NGR motif and its application in drug development for angiogenesis-dependent diseases. Furthermore, we discuss the time-dependent transition of NGR to isoDGR in natural proteins, such as fibronectins, and its potential role of as a "molecular timer" for generating new binding sites for integrins impli-cated in angiogenesis.

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