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-α 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 0.7 Å for GNGRG and 0.5 Å 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.