Disulfide Bond Formation in Ngr Fiber-modified Adenovirus is Essential for Retargeting to Aminopeptidase N.
From: Laboratory for Genotoxic Agents, Division of Molecular Biology, Ruer Bosković Institute, Bijenicka 54, 10000 Zagreb, Croatia.
Biochemical and biophysical research communications
- Publish Date: Sep 2006
- ISSN: 0006-291X
- Volume: 348
- Issue: 1
- Pages: 278-87
- Medium: Print
- Language: English
- Citation (JAMA): Majhen Dragomira, Gabrilovac Jelka, Eloit Marc, et al. Disulfide Bond Formation in Ngr Fiber-modified Adenovirus is Essential for Retargeting to Aminopeptidase N.. Biochem. Biophys. Res. Commun. Sep 2006;348:278-87
Abstract
The peptide motif NGR (asparagine-glycine-arginine) is known to bind to aminopeptidase 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.
Mesh Headings (Keywords): Adenoviridae, Amino Acid Motifs, Amino Acid Sequence, Antigens, CD13, Binding Sites, Capsid Proteins, Cell Line, Cysteine, Disulfides, Gene Transfer Techniques, Genetic Vectors, Humans, Integrin alphaVbeta3, Molecular Sequence Data, Protein Binding, Substrate Specificity, Transduction, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 16876116
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