jeffmartell.bsky.social
Jeff Martell
@jeffmartell.bsky.social
110 followers 130 following 31 posts
Assistant Professor, UW-Madison Chemistry. Group website: http://martellgroup.chem.wisc.edu.
martellgroup.chem.wisc.edu.
Posts Media Videos Starter Packs
Pinned
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 14
Excited to share our new preprint, which was years in the making! chemrxiv.org/engage/chemr...
New reactions are typically developed by trial and error. How can we speed up this process? Read on to learn how we used DNA scaffolding to perform >500,000 parallel reactions on attomole scale.
1/n
DNA-Scaffolded Ultrahigh-Throughput Reaction Screening
Discovering and optimizing reactions is central to synthetic chemistry. However, chemical reactions are traditionally screened using relatively low-throughput methods, prohibiting exploration of diver...
chemrxiv.org
1 18 37
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · 20d
Congratulations Pete, Zach, and team!
jakeyeston.bsky.social
Jake Yeston @jakeyeston.bsky.social · 20d
In @science.org this week @zachwickens.bsky.social and collaborators find a way to do Z-selective elimination using thianthrenium chemistry in a versatile route to Z olefins.

chemsky 🧪

www.science.org/doi/10.1126/...
Stereo-reversed E2 unlocks Z-selective C–H functionalization
The stereoselective functionalization of C–H bonds represents a central challenge in modern organic synthesis. Despite decades of innovation in C–H activation chemistry, methods for Z-selective functi...
www.science.org
2 8
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · 22d
Congratulations @genlichem.bsky.social and Xiao! Very clever probe design.
christhechang.bsky.social
Chris Chang @christhechang.bsky.social · 22d
Happy to share our latest in @jacs.acspublications.org led by Xiao and @genlichem.bsky.social on a new activity-based sensing probe for Cu(I) using a fast alkyne-directed cleavage reaction to discover Mn-sensitized #cuproptosis as a novel type of metal-metal crosstalk! pubs.acs.org/doi/abs/10.1...
An Alkyne-Directed Cleavage Approach for Activity-Based Cu(I) Sensing Reveals Manganese-Promoted Sensitization of Cuproptosis
Copper is an essential element for sustaining life. However, disruptions in copper homeostasis underpin disease, as illustrated by cuproptosis, an emerging form of cell death resulting from aberrant a...
pubs.acs.org
4
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Sep 5
Congratulations, Philip!
1
Reposted by Jeff Martell
philiplampkin.bsky.social
Philip @philiplampkin.bsky.social · Sep 5
My work assessing the effect of preorganization on dihydrazide activity is out in @jacs.acspublications.org. We find that dihydrazides with flexible tethers can replicate much of the catalytic activity of complex dihydrazides with preorganized foldamer scaffolds. #Chemsky

doi.org/10.1021/jacs...
Bifunctional Catalysis of Aldol Reactions by Foldamer Dihydrazides: Assessment of Conformational Preorganization
We previously reported that molecules containing two cyclic hydrazide units connected by a polymethylene linker could catalyze aldol condensations via a bifunctional mechanism. One hydrazide apparentl...
doi.org
1 2 7
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
Congrats to Ashley Ogorek and @shubha-pani.bsky.social‬, who co-led this study, as well as the entire team: Eli, Jelena, Yichong, Fernando, Rachel, @xuhuihuangchem.bsky.social‬. This was a really fun collaboration with ‪@chembiobryan.bsky.social‬ - stay tuned for more to come!

/end
1 3
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
The enhanced bioorthogonality of the bCP ester enabled us to perform spatially-resolved RNA proximity labeling and RNA sequencing, including in human cells lines with high endogenous esterase activity.

9/n
1 1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
The pCP / evolved BS2 pair performs well in multiple sub-compartments of mammalian cells.

8/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
We teamed up with @xuhuihuangchem.bsky.social to perform structural modeling and substrate docking to gain insights into the beneficial mutations.

7/n
1 1 1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
Using DEEPMACh, we evolved BS2 esterase to increase activity toward pCP esters more than 230-fold.

6/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
To overcome this challenge, we developed a new platform, Directed Evolution of Enzymes via Masked Acid Chloride Probes ("DEEPMACh”). DEEPMACh combines yeast surface display with masked acylating probes, enabling rapid screening of >40 million enzyme mutants.

5/n
1 1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
…BS2 esterase shows very low activity toward the pCP ester.

4/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
The methylcyclopropyl (mCP) ester protecting group together with BS2 esterase has been applied as a bioorthogonal system, but background unmasking of mCP occurs in mammalian cells. We found that the bulkier phenylCP group was much more bioorthogonal! However…

3/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
Context: combining bioorthogonal protecting groups with localized catalysts that unmask them is a powerful approach to modulate molecular activity. However, existing protecting groups are insufficiently bioorthogonal, or the catalysts that unmask them cannot be genetically targeted. 2/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 28
Excited to share a new pre-print on a joint study between my group and @chembiobryan.bsky.social‬! Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling. chemrxiv.org/engage/chemr...
1/n
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 ...
chemrxiv.org
2 11 27
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 23
Thanks, Neel!
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 23
Thanks, Chang!
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 23
Thank you! We didn't run into mixing/order of addition issues. Nearly all components are already on DNA, and we add Cu last to commence the reaction. For mixing, we did vortexing then centrifugation, which worked well for our 20 uL scale reactions.
1
Reposted by Jeff Martell
tehshik.bsky.social
Tehshik Yoon @tehshik.bsky.social · Aug 22
Really proud of Riley's preprint on a new class of chiral Lewis acid photocatalysts. This project benefitted from a terrific collab with @chemguyeli.bsky.social chemrxiv.org/engage/chemr...
2 4 36
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 18
Congratulations, Phill! Very well-deserved!
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 14
Thanks especially to Matt and Beck for collaborating with us to merge our platform with data science and ML, and to Josh and Daniel (‪@coonlab.bsky.social‬) for performing essential mass spec characterization of the DNA-small molecule conjugates.‬‬

/end
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 14
Big congrats to co-1st authors Caleb Cox and @edwardpimentel.bsky.social‬ who showed incredible persistence and creativity, and to all co-authors: Beck Miller, Daniel Nesbitt, Justice LeMonds, @ethan-hartman-125.bsky.social‬, Tate Hancock, Robert Kennedy, Josh Coon, and Matt Sigman.

11/n
3
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 14
Overall, we believe this platform opens fundamentally new opportunities in data-driven discovery, optimization, and mechanistic understanding of synergistic catalytic reactions. There are many new directions we’re excited to explore – stay tuned for more in the coming years!

10/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 14
Excitingly, we observed correlation between ML predicted DNA nanoscaffold yields and experimental DNA-free reactions, including for kinetic time courses and for reactants not represented in the original DNA nanoscaffold library.

9/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 14
We teamed up with Matt Sigman and Beck Miller to use data science in library design and to combine our datasets with ML to generate predictive models. The model covers 18,000 reactant combinations under many reaction conditions.

8/n
1
jeffmartell.bsky.social
Jeff Martell @jeffmartell.bsky.social · Aug 14
Using our platform, one researcher performed >500,000 reactions in parallel with less than 3 days of bench time. By incorporating standards and calibration curves, we obtained precise DNA-scaffolded reaction yields using DNA sequencing.

7/n
1