Tailoring Chimeric Ligands for Studying and Biasing ErbB Receptor Family Interactions
Name
Imperiali_Tailoring chimeric.pdf
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Author(s)
Krueger, Andrew T.
Kroll, Carsten
Sanchez, Edgar
Imperiali, Barbara
Griffith, Linda G
Date Issued
January 2014
Journal
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
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1002/anie.201307869
