Synthetic T‑Cell Receptor-like Protein Behaves as a Janus Particle in Solution

Protein engineering enables the creation of tailor-made proteins for a variety of applications. ImmTACs stand out as promising therapeutics for cancer and other treatments while also presenting unique challenges for stability, formulation, and delivery. We have shown that ImmTACs behave as Janus par...

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Veröffentlicht in:Journal of the American Chemical Society 2025-01, Vol.147 (1), p.247-256
Hauptverfasser: Sakamoto-Rablah, Emily, Bye, Jordan, Modak, Arghya, Hooker, Andrew, Uddin, Shahid, McManus, Jennifer J.
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container_end_page 256
container_issue 1
container_start_page 247
container_title Journal of the American Chemical Society
container_volume 147
creator Sakamoto-Rablah, Emily
Bye, Jordan
Modak, Arghya
Hooker, Andrew
Uddin, Shahid
McManus, Jennifer J.
description Protein engineering enables the creation of tailor-made proteins for a variety of applications. ImmTACs stand out as promising therapeutics for cancer and other treatments while also presenting unique challenges for stability, formulation, and delivery. We have shown that ImmTACs behave as Janus particles in solution, leading to self-association at low concentrations, even when the average protein–protein interactions suggest that the molecule should be stable. The formation of small but stable oligomers was confirmed by static and dynamic light scattering and analytical ultracentrifugation. Modeling of the structure using AlphaFold leads to a rational explanation for this behavior, consistent with the Janus particle assembly observed for inverse patchy particles.
doi_str_mv 10.1021/jacs.4c08932
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subjects Models, Molecular
Particle Size
Protein Engineering
Receptors, Antigen, T-Cell - chemistry
Solutions
title Synthetic T‑Cell Receptor-like Protein Behaves as a Janus Particle in Solution
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