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

Autori
Majhen, Dragomira ; Gabrilovac, Jelka ; Eloit, Marc ; Richardson, Jennifer ; Ambriović-Ristov, Andreja

Izvornik
Biochemical and Biophysical Research Communications (0006-291X) 348 (2006); 278-287

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
adenovirus type 5; retargeting; NGR; aminopeptidase N; integrin alpha v beta 3; disulfide bond

Sažetak
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 alpha v beta 3 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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA