tfw you put out a postdoc ad

@CKadoch @kadochlab @DanaFarber Thanks Cigall!

@harveyjberger @DanaFarber Thank you Harvey!

RT @Sadagopan_A: I've really enjoyed working with Will the past few years and would highly recommend his lab to anyone interested in chem b…

@buret_12 yes!

Grateful to everyone who helped along the way—my colleagues, mentors, daycare workers, and especially my family. Thank you all for your support in helping me land my dream job!

@DrMikeBooth @afederation @disha_kashyap_ @milnetom68 @chem_in_cells @OxfordChemistry @UCLChemistry @SchreiberStuart @J_A_C_S Yes, I've had a few folks email me that they've tried some versions of this (adding JQ1 to this or that molecule) and seems to work pretty robustly in others hands too! I think your nucleic acid application is perfect.

Fascinating work showing that the covalent addition of a nuclear importing compound, JQ1, to therapeutic oligonucleotides enhances their activities by enhancing nuclear penetration.

@allisonoconn @DanaFarber Congrats Allison!

It's odd that even though our bifunctionals targeted different proteins, the same spiro linker had some of the highest activity in either case. Maybe chance, maybe not. Something about these short, rigid linkers might encourage cooperativity when the orientations are just right.

@iskander Here's a relevant publication on inhibiting PPIs like the one you're proposing with these genetically encoded macrocycles.

This first-in-class CCNE1 degrader from Monte Rosa is really impressive. It's a molecular glue that finds a shallow pocket on CCNE1 and displays cooperative binding to CRBN, w/ EC50 of 3 nM for the ternary complex. Highly specific CCNE1 degradation.

@Caroline_Bartma @vineethvengayil I feel like theoretically it's possible, but only by altering the way the protein is digested. Fick's law: In=Out. Protein produced = Protein degraded at steady state. So a PROTAC could transiently increase MHC presentation as the levels are falling, but not permanently.