Regina So

Aerobic glycolysis promotes NLRP3 inflammasome activation via NLRP3 lactylation Liu et al. reveal that lactate, an aerobic glycolysis product, promotes NLRP3 inflammasome activation and pyroptosis. NLRP3 is identified as a target of lactylation, and K24 and K565 have potential to...

#WeekendRead! #ImmunometabolismPower! #InflammasomePower! Liu, Yin &co show @cp-cellchembiol that lactate downstream of aerobic glycolysis is used to directly lactylates NLRP3 increasing ASC recruitment and inflammasome activation, which exacerbates lethality in sepsis! www.cell.com/cell-chemica...

📣 Thrilled to announce our incredible speaker lineup for the 2026 edition of #ETOC Online Symposium on April 29-30th.🗓️ Join us by registering today and to stay up-to-date! : tinyurl.com/ETOC2026-reg... (1/3)

Today is #WorldCancerDay

~1 in 5 people will develop #cancer in their lifetime

Each diagnosis affects not just one person, but families, communities, and futures

Grateful today for patients, clinicians, researchers & advocates - and to appreciate that progress depends on acting together

#WCD2026

Excited to share our latest preprint on work led by postdoc Robert Lusi (@rflusi.bsky.social)! Introducing ALTER (AGO-Led Targeted Editing of RNA) for non-downregulatory RNA manipulation by repurposing hAGO2, non-immunogenic and capitalizing on evolution. www.biorxiv.org/content/10.6...

#lcsosynthesisproblem #lcsosynthesisproblem | LCSO Lab SmI₂ enjoyers will not want to miss this week's #LCSOSynthesisProblem, where Najung challenged us to the total synthesis of Aberrarone by Xia, Ding, and co-workers. Check it out here 👉 https://lnkd.in...

And the next edition of #LCSOSynthesisProblem
www.linkedin.com/feed/update/...

Thiol-Free Sulfenylation Redefined: A Single-Atom Transfer Pathway to Symmetrical Di(hetero)arylthioethers via B(C6F5)3 Catalysis Diarylated thioethers are privileged scaffolds found across pharmaceuticals, functional materials, and molecular electronics. Conventional approaches to these motifs, typically via C–H functionalizati...

Congratulations to the team on our latest paper published in @jacs.acspublications.org @cardiffuni.bsky.social

pubs.acs.org/doi/10.1021/...

B cell-intrinsic IL-2 signaling regulates inflammation by promoting IL-10 expression in CD25+ age-associated B cells B cells transiently increase interleukin (IL)-2 receptor expression upon activation. Gauthier et al. examine the B cell-intrinsic role of IL-2 and define an IL-2-MAF axis that promotes the differentia...

#WeekendRead! #FirstLove #IL2power #IL10power #InterferonPower! Delaloy, Gauthier &co show @cp-immunity.bsky.social that IL2 favors a regulatory program in B cells that, together IFNg, induces IL10 production, protecting against neuroinflammation! Exciting paper 🤗! www.cell.com/immunity/ful...

Hallmarks of cancer—Then and now, and beyond Hanahan revisits the evolving framework of cancer hallmarks, synthesizing 25 years of conceptual refinement into a multidimensional view of tumor biology. This review highlights how aberrant capabilit...

Follow up to Doug Hanahan’s visionary article about the stages of cancer development from back in the 1990s

www.cell.com/cell/fulltex...

The last work of Clément TANGUY and Emma Robert on the formal total synthesis of Strictamine is now published in @helvchimacta.bsky.social !
onlinelibrary.wiley.com/doi/10.1002/...

Not new, but a new to us update:

The first preprint out of my lab! We joined forces with @kinasekid.bsky.social @jasonzxzhang.bsky.social and David Baker to study protein phosphorylation! Congrats to Isabella from my lab on her first first author paper! tinyurl.com/43jwwfua

Science update from my postdoc Peiyuan Chai - his work “glycoRNA complexed with heparan sulfate regulates VEGF-A signaling” is now published @nature.com uncovering a new layer or glycoRNA-regulation of growth factor mediated control physiological processes rdcu.be/e1bBX

These peptides have not been shown to cure or treat anything. Safety hasn't been established. Yet, many of the people taking stacks of them, injecting into their bloodstream, are the same ones who are against vaccines. nymag.com/intelligence...

De novo design of potent CRISPR–Cas13 inhibitors - Nature Chemical Biology Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-edi...

Finally out 🎉
New paper in Nature Chemical Biology!

Using RF-diffusion, we designed protein inhibitors that bind the CRISPR Cas13a active site, something very hard to find in nature.

Thanks to everyone involved for the hard work! 👏

www.nature.com/articles/s41...

Headed to the Spring ACS Meeting? 👀

Check out these grids for all the exciting talks and events sponsored by the Division of Organic Chemistry. Your schedule just got a glow-up 🧪🔥

📢 NEW #ChemSciCovers

'Unveiling the molecular dynamics of a nitrile-containing 5-lipoxygenase-activating protein antagonist in primary macrophages through Raman spectroscopy' by Juergen Popp et al.

🔗 doi.org/10.1039/D5SC...

Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling Combining bioorthogonal protecting groups with localized catalysts that can unmask them is a powerful approach to spatially and temporally modulate molecular activity. Enzymes are appealing catalysts ...

Enzyme catalyzed bioorthogonal chemistry published at ACS Cent Sci

pubs.acs.org/doi/10.1021/...

Radical S-Adenosyl-l-Methionine Oxygenase DarE Forms Ether Bond via a Partially Delocalized Tryptophan Cβ Radical Darobactins are ribosomally synthesized and post-translationally modified peptides (RiPPs) with potent activity against Gram-negative pathogens. Their antibiotic function depends on a distinctive β-strand architecture stabilized by an ether cross-link between two tryptophan residues. Unlike most ether linkages in natural products, which arise from hydroxylated precursors, the darobactin ether bond is formed between two unmodified Trp residues by the radical S-adenosyl-l-methionine (SAM) enzyme DarE. DarE catalyzes both O-insertion and ether bond formation using molecular oxygen as a cosubstrate, but its catalytic mechanism remains largely unexplored. Here, we report detection and characterization of a key radical intermediate at the Cβ position of W3 (W3-Cβ•) using isotopically labeled DarA, kinetic analysis, and spectroscopy methods including EPR, ENDOR, and HYSCORE. Similar radical species were also observed in reactions with W3 variants of DarA. These results provide direct evidence that DarE catalyzes ether cross-link formation through reaction of the W3-Cβ• intermediate with O2, revealing an unprecedented radical-mediated strategy for O-atom incorporation in RiPP biosynthesis.

Cβ radical to construct Trp ether cross-link pubs.acs.org/doi/10.1021/...

Create Science organic lec, lab and beyond

New web page drop: regcsoblog.wordpress.com

Late-stage halogen swapping from the Renata group! "Total Synthesis of Allocyclinone A via Late-Stage Halogen Swapping"
chemrxiv.org/doi/full/10....

Late-Stage Diversification of Native Tryptophan-Containing Peptides and Peptide Drugs through Nitrogen Atom Insertion Peptide drugs are a powerful modality in modern drug discovery. Synthetic methods that enable the late-stage diversification of native peptides through amino acid-specific modifications are thus in hi...

Cool read: Late-Stage Diversification of Native Tryptophan-Containing Peptides and Peptide Drugs through Nitrogen Atom Insertion pubs.acs.org/doi/10.1021/...

Structure-Guided Semisynthesis of Blasticidin S–Amicetin Chimeras as Selective Ribosome Inhibitors Peptidyl nucleosides are broad-acting inhibitors, but their dense functionality and complex reactivity have historically limited the modification of these scaffolds. Guided by structural overlays and ...

From cytotoxic natural products to antibiotic leads: A semisynthetic route to blasticidin S scaffolds with high antibiotic potency and reduced cytotoxicity pubs.acs.org/doi/10.1021/...

Photocatalytic coupling of unprotected sugars and N-heteroarenes - Nature Synthesis The synthesis of unprotected C-heteroaryl glycosides is challenging because of the lack of methods to utilize native saccharides as substrates. Now these compounds, capped as redox-active glycosyl sul...

Now online:

Article by Eric Chun Yong Chan, Ming Joo Koh & co-workers

Photocatalytic coupling of unprotected sugars and N-heteroarenes

www.nature.com/articles/s44... ($)
#Chemsky

Good Sunday, all! Here is the curated weekly collection of papers in #cancermetabolism and #mitochondrialbiology. Don't miss it; find it here: biomed.news/bims-camemi/... Biomed News #keepreading

"It's very simple to be happy. But it's very difficult to be simple." - Rabindranath Tagore

The O-GlcNAc Database just got a major upgrade!

New design + new tools
OGT & OGA variant pages
Ontology-based literature search
CytOVS for MS data integration

Made possible by support from @bwfund.bsky.social

oglcnac.mcw.edu

#OGlcNAc #glycotime #database

Happy to share that our seminal work on waixenicin A derivatization is now covered by a provisional patent:
“Waixenicin A Derivatives as Neuroprotective Agents against Hypoxic Ischemic Brain Injury Through TRPM7 Blockade.”

Continuous Hypermutation and Evolution of Luciferase Variants Several luciferases have been developed for imaging and biosensing, and the collection continues to grow as new applications are pursued. The current workflow for luciferase optimization, while successful, remains laborious and inefficient. Mutant libraries are generated in vitro and screened, “winning” mutants are picked by hand, and the isolated sequences are subjected to additional rounds of mutagenesis and screening. Here, we present a streamlined platform for luciferase engineering that removes the need for manual library generation during each cycle. We purposed an orthogonal DNA replication (OrthoRep) system for continuous hypermutation of a well-known luciferase (GeNL). Short cycles of culturing and screening were sufficient to evolve the enzyme, with no repetitive manual library generation necessary. New GeNL variants were identified that exhibit improved light outputs with a noncognate and inexpensive luciferin. We further characterized the novel luciferases in cell models. Collectively this work establishes OrthoRep and continuous hypermutation as a viable method to engineer luciferases, and sets the stage for more rapid development of bioluminescent reporters.

Continuous Hypermutation and Evolution of Luciferase Variants: pubs.acs.org/doi/10.1021/...

GLYCO-BUILD: an enzymatic pipeline for the synthesis of peptides carrying eukaryotic N-glycans - Nature Communications Rossi and colleagues assemble an in vitro enzymatic pipeline using enzymes from distinct domains of life to recapitulate eukaryotic N-glycosylation. This work advances the synthesis of bespoke glycope...

Phenomenal #glycotime by Lorenzo Rossi, @j-a-n-alexander.bsky.social, @asramirez.bsky.social and Kaspar Locher ⬇️ shows a pipeline for building THE glycoform you want with unprecedented yields!

Now you can design your glycoform with GlycoShape and make it with Glyco-BUILD 👏

doi.org/10.1038/s414...

Fun collaboration with @thexavierlab.bsky.social and Ribbeck groups to figure out how this human lectin plays multiple roles in controlling the #microbiome: stabilizing the mucus barrier and reducing bacteria that breach it. news.mit.edu/2026/protein... #glycotime

Thrilled to be able to finally post my first adventure into secondary metabolism!:

Flavoaffinins, Elusive Cellulose-Binding Natural Products from an Anaerobic Bacterium

pubs.acs.org/doi/full/10....

Co-authors: Ruocheng Yu, f. undergrad Jessie Lee, @katherinem.bsky.social , and Emily Balskus!

Catalytically competent nickel(I)–isocyanide compounds for cross-coupling reactions Nature Catalysis, Published online: 14 January 2026; doi:10.1038/s41929-025-01473-9Nickel-catalysed cross-coupling reactions generally use Ni(II) or Ni(0) precatalysts. Here the authors report thermally stable dinuclear Ni(I) complexes with commercial isocyanide ligands for the efficient catalysis in Kumada, Suzuki–Miyaura and Buchwald–Hartwig cross-coupling reactions.

New online! Catalytically competent nickel(I)–isocyanide compounds for cross-coupling reactions