Tailoring Chimeric Ligands for Studying and Biasing ErbB Receptor Family Interactions
Author(s)
Krueger, Andrew T.; Kroll, Carsten; Sanchez, Edgar; Imperiali, Barbara; Griffith, Linda G
DownloadImperiali_Tailoring chimeric.pdf (1.105Mb)
OPEN_ACCESS_POLICY
Open Access Policy
Creative Commons Attribution-Noncommercial-Share Alike
Terms of use
Metadata
Show full item recordAbstract
Described is the development and application of a versatile semisynthetic strategy, based on a combination of sortase-mediated coupling and tetrazine ligation chemistry, which can be exploited for the efficient incorporation of tunable functionality into chimeric recombinant proteins. To demonstrate the scope of the method, the assembly of a set of bivalent ligands, which integrate members of the epidermal growth factor (EGF) ligand family, is described. By using a series of bivalent EGFs with variable intraligand spacing, the differences in structure were correlated with the ability to bias signaling in the ErbB receptor family in a cell motility assay. Biasing away from EGFR-HER2 dimerization with a bivalent EGF was observed to reduce cell motility in an intraligand distance-dependent fashion, thus demonstrating the utility of the approach for acutely perturbing receptor-mediated cell signaling pathways.
Date issued
2014-01Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of ChemistryJournal
Angewandte Chemie International Edition
Publisher
Wiley Blackwell
Citation
Krueger, Andrew T., Carsten Kroll, Edgar Sanchez, Linda G. Griffith, and Barbara Imperiali. “Tailoring Chimeric Ligands for Studying and Biasing ErbB Receptor Family Interactions.” Angewandte Chemie International Edition 53, no. 10 (January 31, 2014): 2662–2666.
Version: Author's final manuscript
ISSN
14337851
1521-3773