The entire paper is supported by (often sub-A resolution) crystal structure magic by @stephcrystallab.bsky.social and Andy Purkiss @crick.ac.uk. My favourite one is of the covalent linkage of WBC10 with Tyr211 - a thing of beauty! Next --> Application!

In parallel, Will performed a covalent, sulfonyl fluoride-targeted fragment screen and found Tyr211 to be especially reactive. Because Tyr211 is around the same binding pocket for our non-covalent inhibitors, we decided to merge these chemotypes. And it worked!

The Bertozzi and Ferguson labs have targeted GALE in the early 2000s (references in the paper!), so we knew it could be drugged. Will did a tour de force fragment screen with colleages @crick.ac.uk at XChem @diamondlightsource.bsky.social. Rounds of iteration got him a good non-covalent inhibitor.

The human UDP-Gal-4-epimerase is important for cellular biosynthesis of UDP-Gal and UDP-GalNAc. Both are important precursors for glycosylation. GALE KO abrogates cellular levels of these metabolites. GALE plays a role in cancer (pubmed.ncbi.nlm.nih.gov/31908526/) - so we decided to drug it!

A special Thank You to @crick.ac.uk and @imperialchemistry.bsky.social, all my friends, mentors, colleagues and collaborators for their amazing support throughout the years - we had (and will continue to have) a lot of fun in London, it is a special place!

A huge Thank You to my amazing lab, everybody has been so supportive.

Dresden is an amazingly collaborative place with a unique, multidisciplinary scientific infrastructure. Our lab will be based in the Faculty of Chemistry and Food Chemistry, with lots of interactions and collabs.

Thank you to our organizers for putting together this program:
@stephanhacker2.bsky.social
Marina Rubini
@borisvauzeilles.bsky.social
@michellefrei17.bsky.social
Hana Macíčková Cahová
@drglycoben.bsky.social
@mlakemeyer.bsky.social
Shixian Lin
@rubenragg.bsky.social
Meghan Lucas
(4/4)

Registration link: www.esboc.org.uk?p=1235

The awesome lineup on 28th May 2025 UK time:

9.30 – 10:00 Craig Markin (Manchester)
10:00 – 10.30 Yi Jin (Manchester)
10.30 – 11:00 Barbara Imperiali (MIT)
11:00 – 11.30 Roman Dembinski (Oakland University)
11.30 – 12:00 Stephen Cochrane (Queen’s University Belfast)

It's a big #glycotime family!