Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy

Akcan, Muharrem, Stroud, Mark R., Hansen, Stacey J., Clark, Richard J., Daly, Norelle L., Craik, David J., and Olson, James M. (2011) Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy. Journal of Medicinal Chemistry, 54 (3). pp. 782-787.

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Abstract

Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mixture of mono-, di-, and trilabeled peptide. Here we report a new chemical entity that bound only a single NIRF molecule. The lysines at positions 15 and 23 were substituted with either alanine or arginine, which resulted in only monolabeled peptide that was functionally equivalent to native chlorotoxin/Cy5.5. We also analyzed the serum stability and serum half-life of cyclized chlorotoxin, which showed an 11 h serum half-life and resulted in a monolabeled product. Based on these data, we propose to advance a monolabeled chlorotoxin to human clinical trials.

Item ID: 27041
Item Type: Article (Research - C1)
ISSN: 1520-4804
Funders: National Institutes of Health (NIH), National Health and Medical Research Council (NHMRC)
Projects and Grants: R01 CA135491-02
Date Deposited: 23 May 2013 01:54
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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