Jalal Uddin

Profiling the proteome-wide selectivity of diverse electrophiles - Nature Chemistry Covalent inhibitors are powerful entities in drug discovery. Now the amino acid selectivity and reactivity of a diverse electrophile library have been assessed proteome-wide using an unbiased workflow...

How can we study target engagement and selectivity of covalent inhibitors? Which electrophilic probes are best suited to study a certain amino acid?

Our study on "Profiling the proteome-wide selectivity of diverse electrophiles" is published in Nature Chemistry.(1/7)

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

A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation Lakemeyer and colleagues analyze the secretome of gut bacteria to identify factors that target host PAR2. They find that the Bacteroides fragilis protease Bfp1 cleaves and activates PAR2, disrupting i...

After a long journey and much hard work from many talented scientists, our paper is finally out. Take a look if you are interested in proteases and host microbe interactions in the gut. www.cell.com/cell-host-mi...

Last chance for early registration for the 2025 Chemical Biology & Physiology Symposium (Dec. 11-13 in Portland, Oregon, USA). Register here:
www.ohsu.edu/school-of-me...
Great program, including talks by Carasco, Chang, Bogyo, Baskin, Swarts, Sampson, Sletten, Dodani, Francis, Urano, Gibbs, etc.

A Two-Step Synthesis of Covalent Genetically-Encoded Libraries of Peptide-Derived Macrocycles (cGELs) enables use of electrophiles with diverse reactivity Genetically-encoded libraries of peptide-derived macrocycles containing electrophile "warheads" (cGELs) can be used to identify potent and selective covalent ligands for protein targets. Such cGELs ar...

Great collaboration with @derda_lab @RatmirDerda just posted to bioRxiv. Check out how to best incorporate electrophiles into cyclic peptides to generate covalent inhibitors. www.biorxiv.org/content/10.1...

Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions Nature Communications - CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human...

rdcu.be/eA0FK

Congrats to postdoc Zhe Zhou on her paper out today in @cp-cellhostmicrobe.bsky.social showing that gut bacteria cross-feed a common dietary antioxidant to produce energy under anaerobic conditions. Thanks to collaborators Angela Jiang and Xiaofang Jiang at NIH.
www.sciencedirect.com/science/arti...

Gas Phase Separation of Modified Peptides for Activity-Based Protein Profiling Profiling the reactivity of the proteome with amino-acid level resolution requires the identification and quantification of reacted peptides in the presence of abundant unmodified peptides. Affinity-b...

An inspiring paper by the group of Jacob Geri in Analytical Chemistry. They present a method for residue-specific #chemoproteomics without the need for an enrichment step. To achieve this, they developed reagents that shift the ion mobility for gas phase separation. pubs.acs.org/doi/full/10....

Probing the proteome - Nature Biotechnology Chemical proteomics has brought rigor to covalent drug discovery and drugs to the clinic. Can it deliver a new generation of drug targets?

A new exciting article in @natbiotech.nature.com highlights the power of chemical proteomics to find druggable pockets on difficult high-value targets. Great insights into applications in covalent and non-covalent drug discovery including clinical development. (1/5) www.nature.com/articles/s41...

Congratulations to Dr. Stavroula Hatzios on this well-deserved recognition! 👏

Activity-Based Protein Profiling of Serine Hydrolases in Bacteria: Methods and Protocols Activity-based protein profiling (ABPP) is a chemoproteomic technique that uses functionalized covalent enzyme inhibitors known as activity-based probes (ABPs) to detect, quantify, and identify active...

Pleased to share our lab-optimized chapter in Methods in Molecular Biology: “Activity-Based Protein Profiling of Serine Hydrolases in Bacteria.” Thanks to @christianslentz.bsky.social .
doi.org/10.1007/978-...

Identification of covalent inhibitors of Staphylococcus aureus serine hydrolases important for virulence and biofilm formation - Nature Communications Staphylococcus aureus is a leading cause of bacteria-associated mortality worldwide. New tools are needed to both image and treat this pathogen. We previously identified a group of S. aureus serine hy...

Our work identifying new covalent inhibitors of Staphylococcus aureus serine hydrolyses from fragment libraries is out! great work from @tulsiupadhyay.bsky.social and our many collaborators, including @christianslentz.bsky.social, @mfellnerlab.bsky.social. #chembio
link.springer.com/article/10.1...

Chemical strategies for targeting lipid pathways in bacterial pathogens Microbial pathogens continue to plague human health and develop resistance to our current frontline treatments. Over the last few decades, there has b…

If you are interested in lipids in bacteria, check out this awesome new review written by my talented student Alyssa Carter, super postdoc Emily Woods and me. #chembio
www.sciencedirect.com/science/arti...

Identification of a secreted protease from Bacteroides fragilis that induces intestinal pain and inflammation by cleavage of PAR2 Protease-activated receptor 2 (PAR2) is a central regulator of intestinal barrier function, inflammation and pain. Upregulated intestinal proteolysis and PAR2-signaling are implicated in inflammatory ...

Excited to report our studies that identified a new serine protease secreted by the gut microbe Bacteroides fragilis that regulates pain and inflammation through PAR2 activation. #ChemBio. Check it out!https://www.biorxiv.org/content/10.1101/2025.01.15.633241v1

Thanks a lot @monaj66.bsky.social 😊

Our paper. Thanks a lot @christianslentz.bsky.social 😊