📣 Our new preprint is out on ‪bioRxiv! De novo chemo-optogenetics through rational small-molecule design and TRAP display #ChemSky #ChemBio #SynBio #Photoswitches www.biorxiv.org/content/10.1... - ThreadSky

shinyatsukiji.bsky.social • 73 days ago

📣 Our new preprint is out on ‪bioRxiv!
De novo chemo-optogenetics through rational small-molecule design and TRAP display
#ChemSky #ChemBio #SynBio #Photoswitches
https://www.biorxiv.org/content/10.1101/2025.04.10.648175v1

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shinyatsukiji.bsky.social•73 days ago

Optical control of biomolecules is a powerful technique in biological research, but current optogenetic tools derived from natural photoreceptor proteins face various limitations. Reengineering these proteins to meet specific research needs remains a major challenge.

shinyatsukiji.bsky.social•73 days ago

Chemo-optogenetics, which uses synthetic photo-responsive ligand–protein tag pairs, offers a promising alternative. However, redesigning existing small-molecule ligands for protein tags into photo-responsive versions with desired properties is also difficult.

shinyatsukiji.bsky.social•73 days ago

In this work, we present a novel strategy that combines the rational design of synthetic photo-switchable molecules with the in vitro selection of artificial protein binders—via TRAP display, an advanced mRNA display—that specifically recognize a particular conformation of these molecules.

shinyatsukiji.bsky.social•73 days ago

Using this approach, we created artificial proteins named AzoTags, which selectively bind to the cis-forms of designed azobenzene derivatives. The trans–cis isomerization of these molecules can be reversibly controlled using two distinct wavelengths of visible light.

shinyatsukiji.bsky.social•73 days ago

The in vitro-selected AzoTags work in mammalian cells! Together with HaloTag, they enable precise, reversible, and repeatable switching of cellular processes using dual light. Several applications are showcased in the manuscript.

shinyatsukiji.bsky.social•73 days ago

Beyond the practical utility of AzoTag tools, this strategy opens exciting new avenues for the de novo development of tailored pairs of synthetic photo-responsive small molecules and artificial protein binders for optical manipulation of biomolecular functions.

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