Balyn Zaro

While PGO may not be as well-suited for broad reactivity profiling as ninhydrin is, its attenuated reactivity suggests it could still be suited for more targeted covalent warhead design. Very excited to see where the field goes this year!

To test whether arginine reactivity can be functionally leveraged, we appended a ninhydrin warhead to a reversible cyclophilin A inhibitor, achieving selective covalent engagement and attenuation of enzymatic activity.

Using this platform, we identified > 6,800 unique reactive arginines across the proteome, enriched in disease-relevant proteins and including residues located in essential catalytic sites.

We developed ninhydrin-based, alkyne probes that selectively modify arginine residues and benchmarked them against current best in class phenylglyoxal (PGO). Ninhydrin probes showed substantially improved proteomic coverage, both by gel-based assays and by chemical proteomics.

Ninhydrin as a covalent warhead for chemical proteomic-enabled discovery and selective engagement of reactive arginines Covalent molecules have emerged as next-generation therapeutics and as powerful tools for perturbing fundamental biological processes. Chemical proteomic methods to screen for reactive proteinaceous a...

Is arginine the new cysteine?! Check out our lab's latest in collaboration with @ianseiple.bsky.social's team where we introduce ninhydrin as a selective covalent warhead and probe targeting reactive arginines.
www.biorxiv.org/content/10.6...

Integrative analysis of mRNA stability regulation uncovers a metastasis-suppressive program in breast cancer Heterogeneity in cancer gene expression is typically linked to genetic and epigenetic alterations, yet post-transcriptional regulation likely influences these patterns as well. However, the quantitati...

Been going back and forth on whether it makes sense to post science in the midst of all that is happening. But here it goes with a couple of days of delay:
www.biorxiv.org/content/10.1...

Excited to see this story finally out! What a fun and collaborative group to work with!

Pervasive and programmed nucleosome distortion patterns on single mammalian chromatin fibers We present a genome-scale method to map the single-molecule co-occupancy of structurally distinct nucleosomes, subnucleosomes, and other protein-DNA interactions via long-read high-resolution adenine ...

Amid concerning times, sharing a bit of positivity: our 1st preprint of 2025 (funded VIA NIH COMMON FUND), heroically led by Marty Yang (@martyyang.bsky.social) w/ huge assist from @genophoria.bsky.social lab. Lots to cover so let’s get this tweetorial started (1/n)! www.biorxiv.org/content/10.1...

Molecular basis of proton sensing by G protein-coupled receptors Howard et al. combine mechanistic deep mutational scanning, cryo-EM, and constant-pH molecular dynamics simulations to provide a holistic view of proton activation in human pH-sensitive GPCRs.

Congrats @willowcoyote.bsky.social @amanglik.bsky.social and all authors on a tour de force dissection of proton-sensing by GPCRs! DMS, cryo-EM, MD -- it has it all! www.cell.com/cell/fulltex...