What can HaloTag do for you?

Triggered fluorogenic labelling?
Molecular recording?
Photo-Chemically Induced Dimerisation?

Philipp Mauker's CHalo motif lets reagents do all three, and more.

Read the preprint here -
doi.org/10.1101/2025...

#chembio #fluorescence #cellbio #SLP

Molecular Recording with HaloTag?
H2O2, GSH, Trx, LAP?

→ multiplexable reagents record diverse enzyme activities ratiometrically, without signal loss

@biorxivpreprint.bsky.social
preprint: doi.org/10.1101/2025...

CHalo Crew again programming with HaloTag!
#chembio #fluorescence #wednesday

Photocaged HaloTag Ligation with red fluorogenic SiR labels:

→ on-demand HaloTag visualisation and tracking

@biorxivpreprint.bsky.social preprint: doi.org/10.1101/2025...

Congrats Philipp Mauker, Joyce Meiring, & the CHalo Crew for again programming with HaloTag!
#chembio #fluorescence #wednesday

Chemically Induced Dimerisation, modular & on-demand:

=> Fast, stepwise reagents for HaloTag-to-SNAP-tag heterodimerisation without a hook effect

Now preprinted: doi.org/10.1101/2025...

Congratulations to Philipp Mauker & the CHalo Crew for programming with HaloTag!
#chembio #fluorescence #friday

For ion-specific photocurrents across membranes: just let ionophores intermingle with photolipids.

A fully modular approach with easy access to large currents.

Stoked that this years-long sleuthing effort led by Peter Pohl is finally out! doi.org/10.1101/2025...

#photopharma #ChemBio #lipidtime

For those who enjoyed the Saturn saga: its Altmetric score is 3x higher than the Nature average, thanks to the 835 of you who reposted & commented. Pat on the back to all! and (although still no reply to email) thanks again to the legendary authors :)

www.altmetric.com/details/1704...

Congrats to our new Doctor Markus!
@m-markus.bsky.social pioneered chromocontrol by ideal efficacy photoswitching (doi.org/10.1101/2024...), TRPC5 photopharma (doi.org/10.1002/anie...), & switch-based photoacoustic imaging (doi.org/10.1002/anie... & doi.org/10.26434/che...) : a tour de force summa!

if only @altmetric.com included @bsky.app posts that paper would be outdoing CNS…

for #chemsky 🧪 honour though: let the other hot mess that is Moonraker console you of the utter seriousness of molecules and #chembio „assays“ even in space.

“science is not restricted to molecules” 😱 the craziest part of this whole space opera

Sorry #chemsky #realtimechem #chembio we are their first stop for more shade 🧪

(from the PubPeer
pubpeer.com/publications...

📯Photoacoustic Imaging Heterodoxy📯

Usually PA dyes are built by *first* taking high-NIR-ε fluorophores, *then* suppressing fluorescence.

@m-markus.bsky.social now argues why this misses the best chemical space for PA agents. PP out soon... stay λ-tuned!

#ChemBio #ChemSky #realtimechem #SciSky

Wishing the Elsevier editors who desk-accepted this all the best for their next career moves.

doi.org/10.1016/j.ij...

See the paper & Supp Notes for the full story of our collaboration community's awesome work - from design, synthesis, switching, cell culture, primary culture, tissue slice, right through to organ sections!

So: the take-home?

Caveat Optogenetics - the chemists are coming for you now!

doi.org/m75j

• works in deep tissue
• translates perfectly across multiple biological models
• 2 x cryo-EM structural rationales
• works in endogenous tissues at nanomolar concs

• favourite: channel is overstimulated at 30 nM under 365 nm? Works perfectly at 385 nm *even up to 300 nM*

=> that's chromocontrol!

So: work off high-affinity scaffolds, but design around an efficacy cliff rather than an affinity cliff.

Now, moderate concentrations will over-saturate every cell's binding sites; but choosing light wavelengths will rheostat bioactivity *to equal degrees in every cell*.

This is **Chromocontrol**

Build a concentration-compensation method: design *self-competitive efficacy photoswitches*.

If their E/Z binding affinities are equal, the overall bioactivity is only determined by the E:Z ratio:

ie the *only* parameter you can reliably control in vivo. Just choose a monochromatic illumination λ!

...even in one target tissue, the reagent dose is different in each cell, and changes over time.

So your bio-effects will be completely different between cells [spatial] and over time, *even when re-applying the same photocontrol wavelengths (same PSS & E/Z ratio)*

🧵4/n

Introducing: Chromocontrol!

our first science Bsky post for 2024 :) #ChemSky #ChemBio

The most important photopharmacology work we've done in years.

Ditched the photoswitch design principles we used since a decade, & started all over again.

And now it will work in vivo.
doi.org/10.1101/2024...

#ChemSky challenge: how do you increase thiol probe reactivity, while *also* increasing selectivity, without target-specific binding?

→ Use a multistep reaction cascade allowing to tune on-target & off-target rates independently, although the rxn chemistries are the same.

doi.org/10.26434/che...