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RT @RolandDunbrack: Demis -- I think AlphaFold3 is really exciting. As Reviewer #3, I got great results from the server. I tried hard to ge….

RT @AChemSynBio: Thankful for this recognition. All credits go to my group's past and present members; I have been truly fortunate to work….

RT @AChemSynBio: We got a story, and it’s electric! 🔌⚡️ .Can electrocatalysis be used to precisely modify a protein….

RT @ACS_DivBioChem: Congratulations to @CraigMCrews on receiving the Kimberly Prize from @NUFeinbergMed for pioneering studies of #PROTACs….

RT @davidrliu: The first in vivo base editing clinical trial outcomes are now reported, following last year’s positive ex vivo base editing….

RT @DanNomura: New @biorxivpreprint from our lab by @Qian37774492 on a covalent 14-3-3 molecular glue with the transcription factors YAP an….

RT @LabRullo: Happy to share our most recent contribution coupling covalency with carbohydrate binding for immune proximity induction. htt….

RT @ChemicalBiology: I worry that this organization will put more pressure on reviewers to focus on the details and put even less focus on….

. we will report platform 2 design principles that enable recruitment of >310 kinases and lysine-based group transfer linkers as Lys is more abundant. These principles will help develop chimeras for writing/erasing any PTMs using inhibitors. Happy to share linkers/knowhow!

Group transfer/proximity-induced labeling chemistries are well known (see Westheimer et al, Hamachi et al). Wyeth (2001) and AstraZeneca (2013) reported thiol-based group transfer for EGFR inhibitors, Thai et al (2020) have called it TMAcs and London et al (2021) CoLDR. Soon.

Conversely, platform 2 chimeras use abundant, ATP-competitive kinase inhibitors. Here, the kinase inhibitor tags kinase (BTK) with target binder (JQ1, a BRD4 binder) using a cysteine-based group transfer chemistry (panel A)—the tagged kinase then phosphorylates BRD4 (panels B, C)

Platform 1 chimeras are not scalable as they require non-inhibitory, allosteric kinase binders that are scarce. This scarcity of non-inhibitory binders is a major roadblock in the field, preventing the rapid development of chimeras for inducing other PTMs/tissue-specific PROTAC.

Using platform 1 chimeras that recruit Abelson kinase (ABL) to EGFR (panel A), we observed signaling-relevant phosphorylations on EGFR (panel B) and activation of downstream signaling (i.e., transcriptional activation, Panel C).

In @ACSCentSci, we report two chimeric molecule platforms to induce tyrosine phosphorylation, a critical PTM. Chimeras (formed by fusing target and kinase binders) force kinase to phosphorylate non-substrate via induced proximity.

RT @wgibson: What if small molecules could allow you to alter protein localization at will?. What if they could allow you to turn on specif….

RT @DanNomura: Excited to see our @ACSCentSci paper published on rational design of molecular glue degraders via a transplantable covalent….

RT @CarolynBertozzi: Crowd at #ACSSpring2023 goes wild celebrating Laura Kiessling ⁦@ChemicalBiology⁩ receiving the Breslow Award 🎉 https:/….

RT @JuliaJoung: Thrilled to share my primary PhD work: a Transcription Factor Atlas for understanding gene regulation and cell engineering….

RT @JSheltzer: Very disappointed to see this new paper in @NatureCancer on a clinical trial with “HDAC6 inhibitor” ricolinostat. The paper….