Disulfide bond formation in NGR fiber-modified adenovirus is essential for retargeting to aminopeptidase N

详细信息    查看全文

• 作者：Dragomira Majhen ; Jelka Gabrilovac ; Marc Eloit ; Jennifer Richardson and Andreja Ambriović ; -Ristov
• 关键词：Adenovirus type 5 ; Retargeting ; NGR ; Aminopeptidase N ; Integrin α ; _vβ ; ₃ ; Disulfide bond
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 出版时间：15 September 2006
• 年：2006
• 卷：348
• 期：1
• 页码：278-287
• 全文大小：223 K

文摘

The peptide motif NGR (asparagine–glycine–arginine) is known to bind to aminopepidase N (APN). We have constructed five adenoviruses (Ads) bearing NGR in the HI loop of the adenoviral fiber protein. We compared the targeting properties of the NGR peptide within different amino acid environments and showed that their cellular receptor(s) were not identical. Ads containing NGR within potentially cyclic sequences flanked by cysteines retargeted viruses mainly to APN, while Ads containing NGR within linear sequences not containing cysteines retargeted Ads mainly to α_vβ₃ integrin, albeit with a lower affinity. Finally, we show evidence that disulfide bond formation within an Ad bearing the CDCNGRCFC sequence is essential for retargeting to APN, suggesting that this sequence does indeed assume a cyclic structure which facilitates NGR binding to APN. Therefore, our study underscores the importance of cysteine residues flanking targeting peptides for not only affinity but also specificity of the retargeted Ad.