Glycine N-Methylation in NGR-Tagged Nanocarriers Prevents Isoaspartate Formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing

作者：Corti Angelo^*; Gasparri Anna Maria; Ghitti Michela; Sacchi Angelina; Sudati Francesco; Fiocchi Martina; Buttiglione Valentina; Perani Laura; Gori Alessandro; Valtorta Silvia; Moresco Rosa Maria; Pastorino Fabio; Ponzoni Mirco; Musco Giovanna; Curnis Flavio

来源：Advanced Functional Materials, 2017, 27(36): 1701245.

DOI：10.1002/adfm.201701245

• deamidation
• enzymes
• molecular docking
• N-methylglycine
• peptides

NGR (asparagine-glycine-arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials, and imaging compounds for cancer treatment and diagnosis. Unfortunately, this motif has a strong propensity to undergo rapid deamidation. This reaction, which converts NGR into isoDGR, is associated with receptor switching from CD13 to integrins, with potentially important manufacturing and pharmacological and toxicological implications. It is found that glycine N-methylation of NGR-tagged nanocarriers completely prevents asparagine deamidation without impairing CD13 recognition. Studies in animal models have shown that the methylated NGR motif can be exploited for delivering radiolabeled compounds and nanocarriers, such as tumor necrosis factor-a-bearing nanogold and liposomal doxorubicin, to tumors with improved selectivity. These findings suggest that this NGR derivative is a stable and efficient tumor-homing ligand that can be used for delivering functional nanomaterials to tumor vasculature.

• 出版日期2017-9-26