Site‐specific encoding of photoactivity in antibodies enables light‐mediated antibody‐antigen binding on live cells

Bridge, Thomas, Shaikh, Saher A, Thomas, Paul, Botta, Joaquin, Mccormick, Peter J and Sachdeva, Amit (2019) Site‐specific encoding of photoactivity in antibodies enables light‐mediated antibody‐antigen binding on live cells. Angewandte Chemie, 58 (50). pp. 17986-17993. ISSN 0044-8249

[img] PDF (Accepted_Manuscript) - Submitted Version
Restricted to Repository staff only until 14 October 2020.

Download (3MB) | Request a copy
[img]
Preview
PDF (Bridge_et_al-2019-Angewandte_Chemie_International_Edition) - Published Version
Available under License Creative Commons Attribution.

Download (4MB) | Preview

Abstract

Antibodies have found applications in several fields, including, medicine, diagnostics, and nanotechnology, yet methods to modulate antibody‐antigen binding using an external agent remain limited. Here, we have developed photoactive antibody fragments by genetic site‐specific replacement of single tyrosine residues with photocaged tyrosine, in an antibody fragment, 7D12. A simple and robust assay is adopted to evaluate the light‐mediated binding of 7D12 mutants to its target, epidermal growth factor receptor (EGFR), on the surface of cancer cells. Presence of photocaged tyrosine reduces 7D12‐EGFR binding affinity by over 20‐fold in two out of three 7D12 mutants studied, and binding is restored upon exposure to 365 nm light. Molecular dynamics simulations explain the difference in effect of photocaging on 7D12‐EGFR interaction among the mutants. Finally, we demonstrate the application of photoactive antibodies in delivering fluorophores to EGFR‐positive live cancer cells in a light‐dependent manner.

Item Type: Article
Faculty \ School: Faculty of Science > School of Chemistry
Faculty of Science
Faculty of Science > School of Pharmacy
Depositing User: LivePure Connector
Date Deposited: 21 Oct 2019 12:30
Last Modified: 03 Jun 2020 23:57
URI: https://ueaeprints.uea.ac.uk/id/eprint/72726
DOI: 10.1002/anie.201908655

Actions (login required)

View Item View Item