iiinova — where your digital self keeps evolving

Jeff Martell @jeffmartell.bsky.social · 17/12/2025

Congratulations, Yamuna and team! This is so cool.

Jeff Martell @jeffmartell.bsky.social · 13/11/2025

Check out our review on DNA-scaffolded catalysis! This link provides free full text access until the end of 2025: authors.elsevier.com/a/1m43W9CpcY.... Big thanks to co-authors @edwardpimentel.bsky.social , Ashley Ogorek, @ethan-hartman-125.bsky.social , and Caleb Cox

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Jeff Martell @jeffmartell.bsky.social · 19/09/2025

Congratulations Pete, Zach, and team!

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Jeff Martell @jeffmartell.bsky.social · 16/09/2025

Congratulations @genlichem.bsky.social and Xiao! Very clever probe design.

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Reposted by Jeff Martell

Philip @philiplampkin.bsky.social · 05/09/2025

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...

doi.org

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...

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

The pCP / evolved BS2 pair performs well in multiple sub-compartments of mammalian cells. 8/n

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

We teamed up with @xuhuihuangchem.bsky.social to perform structural modeling and substrate docking to gain insights into the beneficial mutations. 7/n

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

Using DEEPMACh, we evolved BS2 esterase to increase activity toward pCP esters more than 230-fold. 6/n

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

…BS2 esterase shows very low activity toward the pCP ester. 4/n

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 28/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 23/08/2025

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.

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Reposted by Jeff Martell

Tehshik Yoon @tehshik.bsky.social · 22/08/2025

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...

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Jeff Martell @jeffmartell.bsky.social · 18/08/2025

Congratulations, Phill! Very well-deserved!

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

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

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

Our approach draws inspiration from the pioneering work of David Liu on DNA-templated substrate coupling to screen for bond-forming reactions, www.nature.com/articles/nat... and the Vipergen Yoctoreactor which brings together 3 components for DNA-encoded small molecule synthesis. 6/n

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

Our platform works by 3 steps: 1) combinatorial self-assembly of a DNA nanoscaffold library, 2) Simultaneous scaffolded reactions and high-throughput selection of product-bearing nanoscaffolds 3) PCR amplification and next-generation DNA sequencing to identify successful reactions conditions. 5/n

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

We wondered whether we could use DNA scaffolding and next-generation DNA sequencing to dramatically increase the throughput, allowing >500,000 reactions to be performed in parallel, with simultaneous reaction analysis by sequencing. 4/n

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

Impressive advances in high-throughput experimentation (HTE) enable ~10^4 reactions to be performed in multi-well plates (www.science.org/doi/10.1126/...). However, this requires individual reaction setup and screening, increasing the analysis time proportionally. 3/n

science.org

Nanomole-scale high-throughput chemistry for the synthesis of complex molecules

Automated technology enables chemical reaction optimization using micrograms of material.

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

Synergistic catalysis can unlock new reactivity, but it presents a multidimensional screening challenge. In the example scenario below, there are >500,000 combinations. 2/n

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Jeff Martell @jeffmartell.bsky.social · 14/08/2025

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

chemrxiv.org

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...

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Jeff Martell @jeffmartell.bsky.social · 18/07/2025

Congratulations, Mark and team!

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Reposted by Jeff Martell

Neel Shah @nshahlab.bsky.social · 21/06/2025

Despite ~20 years in/around #chembio research, I went to my first Bioorganic GRC this week. This community is amazing and so supportive. I feel energized (and tired, lol) and find myself rooting for the next generation of chemical biologists. Sooooo much awesome science - We can’t/won’t be stopped!

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