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Immunogenic and structural properties of the Asn-Gly-Arg (NGR) tumor neovasculature-homing motif.
- Source :
-
Molecular immunology [Mol Immunol] 2006 Apr; Vol. 43 (10), pp. 1509-18. Date of Electronic Publication: 2005 Dec 07. - Publication Year :
- 2006
-
Abstract
- Tumor homing peptides containing the NGR motif, such as CNGRC and GNGRG, have been used for delivering cytokines, chemotherapeutic drugs, apoptotic peptides, and liposomes to a CD13 isoform expressed in tumor blood vessels. In view of the potential clinical applications of these drugs and considering the risk that NGR peptides could elicit blocking antibodies we have investigated the immunogenic properties of CNGRC and GNGRG in mice and rabbits, using various products containing these residues and different administration schedules. The results suggest that the immunogenicity of the NGR motif is very low, even when it is conjugated to tumor necrosis factor-alpha or to highly immunogenic carrier proteins. Molecular dynamics simulation experiments showed that both peptides have a strong propensity to populate a turn conformation. Superposition of predicted structures to the CTGNGRGEWKC loop of the 5th type I repeat of human fibronectin, a protein that contains four NGR motives, showed that the root mean square deviation of backbones was 0.7A for GNGRG and 0.5A for NGR. These results suggest that NGR peptides could mimic from an immunological point of view a "self" structure, likely the GNGRG loop of fibronectin, with important implications for the use of these targeting peptides in patients.
- Subjects :
- Amino Acid Motifs immunology
Amino Acid Sequence
Angiogenesis Inhibitors administration & dosage
Animals
Fibronectins immunology
Mice
Molecular Sequence Data
Oligopeptides chemistry
Peptides chemistry
Peptides, Cyclic chemistry
Protein Conformation
Rabbits
Antineoplastic Agents administration & dosage
Neoplasms blood supply
Oligopeptides immunology
Peptides immunology
Peptides, Cyclic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0161-5890
- Volume :
- 43
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16337683
- Full Text :
- https://doi.org/10.1016/j.molimm.2005.10.009