@ blue skies, there is .a collection of 150 chemical biologist accounts to make it really easy to jump start your #ChemBio network. Why not at Twitter? :( no wonder people are leaving here.

Please retweet #realtimechem #FluorescenceFriday @MolSwitches @photopharma_lit @RealTimeChem to spread the news out to the #ChemBio and OC / probes world.

The details in this paper of the week! Phosphonorhodamines and lots of astute discussion from Evan Miller at UCB. Enjoy!. Hard to justify any more why we aren‘t using them as a default fluorophore… be warned…. #fluorescence_friday.

Want to photo-stabilise microtubules? just write and we can send you CouEpo. Some tool creation papers make new concepts. Others fill in the practical gaps for things that need to exist but don‘t yet. Carina‘s @angew_chem is one of those. Congrats!

RT @jenheemstra: Every person who you mentor is a unique individual, and none of them are you. Mentoring isn’t about sharing what you woul….

Paper of the week: a no-BS rundown of why most TrxR covalent inhibitors are poor quality, then a light towards high quality chemical probes for oxidorectases (doorstop pocket). Great @ACSBioMed J Med Chem by Angelucci, Williams & @PashaUIC . Enjoy -

RT @ChemistryViews: Unique Patterns of Thiol-Mediated Cellular Uptake: Two existing exchange networks and a new repressor pathway discovere….

RT @matile_group: In our new paper in ChemistryEurope - the upcoming GOA flagship journal of the European Chemical Societies - we explore c….

RT @Samba_Banala: Paper out! My project on new photocages with @rhodamine110 is published in @J_A_C_S. The new photocage (“ABC cage”) is us….

RT @angew_chem: Azobenzene molecular switches are repurposed for photoacoustic imaging: picosecond electronic relaxation drives thousand-fo….

classic🧵12/11.There are many grey zones, or situations where "efficacy or affinity switch" discussion is not appropriate. But our aim is not a comprehensive review: rather an experimental demo plus a thought-provoking concept outlook. That said, dive in & don't hold back! o&o.

It's Twitter so much detail has been skipped; but this'll be the last tweet - see paper & Supp Notes for the full story. Thanks so much to all our collaboration community! and please email / post any feedback; looking forward to it!. 🧵11/11

• works in endogenous tissues at nanomolar concs.• personal favourite: though overstimulated at 30 nM under 365 nm, is tuned down perfectly at 385 nm *even when concentration is raised to 300 nM*. ⟶ now that's chromodosing! (not chromo+dose-ing). 🧵10/n

But, while it can always be argued that new papers are "just" re-discovering the obvious or the past, we think this paper adds a few sticks to the fire. • works in deep tissue.• translates perfectly across multiple biological models.• 2 x cryo-EM structural rationales. 🧵9/n.

Of course this builds on big shoulders; shoutouts to Rob Leurs, Pau Gorostiza, Michael Decker, Wiktor Szymanski, @FeringaLab, @DirkTrauner, James Frank, and many more (see Supp Info). Particularly Rob Leurs' 2019 work at 🧵8/n.

For self-competing E&Z isomers, as long as their binding affinities are nearly equal, the overall bioactivity they apply will be purely determined by the E:Z ratio:. Which is the *only* parameter you can reliably control in vivo. Just choose a monochromatic illumination λ!. 🧵7/n

How to escape the concentration-dependency of biological effect?. Make a system-internal (intrinsic) compensation method. Self-competitive photoswitches.

since the whole point of photopharmacology is to control biology in space and in time, this is a critical systematic problem!. 🧵5/n.

. mean that even in one target tissue, the dose is different in each cell, and changes over time. So your bio-effect will be completely different, even when applying the same wavelength (same PSS & E/Z ratio), . *and differs both in space and in time*

Usually, photopharmacology tries to optimise photoswitching between a high-activity isomer and a low-activity isomer. This is fine for cell culture because all cells see the same drug concentration. But in vivo, no: ADME-PK, variable distance to blood vessels, animals. 🧵3/n.