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John Schneekloth (Jay) @jschneek.bsky.social · Jun 25

Honored to see that our collaborative work with Pratyush Tiwary and Adrian Ferré-D'Amaré on the ZTP riboswitch was selected as a very important paper by @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...

Machine Learning‐Augmented Molecular Dynamics Simulations (MD) Reveal Insights Into the Disconnect Between Affinity and Activation of ZTP Riboswitch Ligands

This study combines computational and experimental approaches to study how natural and synthetic small molecules interact with the ZTP riboswitch, a bacterial RNA element that regulates gene expressi....

onlinelibrary.wiley.com

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John Schneekloth (Jay) @jschneek.bsky.social · May 28

Hear-hear! Science making amazing progress and saving lives despite increasing barriers is something to be celebrated.

Jordan Meier @doc-jlmeier.bsky.social · May 28

This piece by George Church in @statnews.com is the best response I've read, key quote (emphasis mine):

"Perhaps it's time to embrace the spirit of anti-complacency and pro-innovation WITHOUT HALLUCINATING A DEPRESSING DECLINE IN THE FACE OF REMARKABLE PROGRESS." 👏

www.statnews.com/2023/02/01/d...

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John Schneekloth (Jay) @jschneek.bsky.social · May 28

Congrats to the people who helped get this across the finish line - Mo Yang, Peri Prestwood, other co-authors, and collaborators Kevin Weeks and Adrian Ferre-D'Amare!

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John Schneekloth (Jay) @jschneek.bsky.social · May 28

We also demonstrate for the first time that bonding interactions between ligands and K+ ions in G4s can exist. These new dyes have increased brightness and performance in imaging relative to TO and TO1-biotin (the dyes Mango II was evolved to bind).

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John Schneekloth (Jay) @jschneek.bsky.social · May 28

Out now in @natchem.nature.com! Lots to unpack here, but in short - we show that SMM enabled fragment based design is useful on RNAs to improve chemical properties like affinity and brightness of fluorophore ligands.

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

Structure-informed design of an ultrabright RNA-activated fluorophore - Nature Chemistry

Fluorogenic RNA aptamers such as Mango are powerful tools for RNA imaging. An ultrabright RNA-activated fluorophore with improved photophysical performance has now been developed using a structure-inf...

www.nature.com

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John Schneekloth (Jay) @jschneek.bsky.social · May 8

New work from the lab - With Pratyush Tiwary and Adrian Ferre-D'Amare, we study ligands that activate the ZTP riboswitch. Experimental and theoretical approaches show that ligand on rates influence activity by non-obvious mechanisms when targeting RNA!

onlinelibrary.wiley.com/doi/10.1002/...

Machine learning‐augmented molecular dynamics simulations (MD) reveal insights into the disconnect between affinity and activation of ZTP riboswitch ligands

The challenge of targeting RNA with small molecules necessitates a better understanding of RNA-ligand interaction mechanisms. However, the dynamic nature of nucleic acids, their ligand-induced stabil...

onlinelibrary.wiley.com

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Reposted by John Schneekloth (Jay)

ACS BIOL: Division of Biochemistry and Chemical Biology @acsbiol.bsky.social · May 6

Congratulations to Evan J. Burke, a grad student in the Krebs and Bollinger labs in Penn State's Department of Chemistry, on being named a 2025 #ACSBIOL Young Investigator!
@jmarbol21.bsky.social

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John Schneekloth (Jay) @jschneek.bsky.social · Apr 30

Another new piece of work from the lab - I played a small role in this really exciting work coming out of the Pearson lab at Sick Kids in Toronto dealing with preclinical studies on CAG repeat instability in Huntington disease. Check it out: www.biorxiv.org/content/10.1...

Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.

Huntington disease (HD) is caused by inherited CAG expansions, which continue expanding somatically in affected brain regions to hasten disease onset and progression. Therapeutically diminishing somat...

www.biorxiv.org

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John Schneekloth (Jay) @jschneek.bsky.social · Apr 25

Hey, check it out - new work from the lab! We report the design of design traceless, reversible small molecule photocrosslinking probes that can be used to photochemically control the translation of mRNAs just using molecular recognition! Congrats to all! onlinelibrary.wiley.com/doi/10.1002/...

Harnessing Molecular Recognition for Small‐Molecule‐Mediated Reversible Photochemical Control Over mRNA Translation

A small molecule ligand undergoes traceless, reversible photocrosslinking to PreQ1 RNA aptamer in a selective manner, dependent on both the RNA sequence/structure and ligand chemical structure. A cag...

onlinelibrary.wiley.com

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Reposted by John Schneekloth (Jay)

Luke Lavis @rhodamine110.bsky.social · Apr 11

We're looking for 1-2 enthusiastic early career chemists to join our Open Chemistry team at @hhmijanelia.bsky.social. Come help us create amazing dyes and share them with the world. Please share with the best recent/soon-to-be B.S. chemists you know! bit.ly/42w8C6N

Research Technician - Open Chemistry

Primary Work Address: 19700 Helix Drive, Ashburn, VA, 20147 Current HHMI Employees, click here to apply via your Workday account. Summary: Open Chemistry is a collaborative research group whose missio...

bit.ly

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John Schneekloth (Jay) @jschneek.bsky.social · Apr 10

I love doing this, especially for the gut check about how your biases and intuition for what will/won't work can be so wrong!

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Reposted by John Schneekloth (Jay)

Jordan Meier @doc-jlmeier.bsky.social · Apr 10

Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost.

www.training.nih.gov/research-tra...

www.training.nih.gov

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John Schneekloth (Jay) @jschneek.bsky.social · Apr 4

New work from my awesome colleague @vidigaljoana.bsky.social!

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

What was that you said? You are looking for new #RNA research to read in the weekend?

You are in luck!

📣 📣 Check out the new preprint from our lab!!!! 📣 📣

www.biorxiv.org/content/10.1...

AGO2 slicing of a domesticated retrotransposon is necessary for normal vasculature development

Argonaute (AGO) mediated slicing of RNA, also known as RNAi, is a highly conserved phenomenon that is evolutionarily linked to the repression of transposons and other repeats. Although RNAi is no long...

www.biorxiv.org

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John Schneekloth (Jay) @jschneek.bsky.social · Apr 3

"rare high energy conformations"

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Reposted by John Schneekloth (Jay)

ACS BIOL: Division of Biochemistry and Chemical Biology @acsbiol.bsky.social · Mar 26

The final #ACSBIOL sessions of #ACSSpring2025 are tomorrow morning, Thursday the 27th:

📰 Current Topics in #Biochem and #ChemBio, Room 31A

👩‍🎓 Undergraduate and Graduate Research, Hal G/H Room 8

Be sure to check out these excellent presentations!

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Reposted by John Schneekloth (Jay)

ACS BIOL: Division of Biochemistry and Chemical Biology @acsbiol.bsky.social · Mar 25

#ACSBIOL Sessions on Wednesday, 26th at #ACSSpring2025:

Morning, Room 31A:
🏆 Eli Lilly Award to @brianliau.bsky.social

Afternoon, Room 31A:
🏆 ACS Chemical Biology Young Investigator Award to @jeremybaskin.bsky.social

Evening, Hall B2/C:
📜 Poster Session, Current Topics

@pubs.acs.org

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John Schneekloth (Jay) @jschneek.bsky.social · Mar 13

Congrats @rche54.bsky.social, nice work!

Ross Cheloha @rche54.bsky.social · Mar 13

Proud to share this work from my group in the intramural research program at NIH! We describe a new kind of conjugate made from a small molecule adenosine analog linked to a GPCR targeting nanobody to make antibody drug conjugates that potently and specifically activate signaling (1/n) 🧪 #chembio

bioRxivpreprint @biorxivpreprint.bsky.social · Mar 12

Nanobody-based conjugates targeting small molecule-binding GPCRs and exhibiting logic-gated signaling https://www.biorxiv.org/content/10.1101/2025.03.07.642093v1

John Schneekloth (Jay) @jschneek.bsky.social · Jan 22

Check out this awesome paper from my colleague @eunayoo.bsky.social about activity-based probes for USP18! www.nature.com/articles/s41...

Chemical tools to define and manipulate interferon-inducible Ubl protease USP18 - Nature Communications

USP18 is a multifunctional cysteine protease involved in IFN pathways. Here, the authors report chemical probes and chemoproteomics platforms that allow to detect and perturb USP18 activity in complex...

www.nature.com

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John Schneekloth (Jay) @jschneek.bsky.social · Dec 19

We often focus on publicizing our work to other scientists but it's just as important to have journalists communicate with non-scientists as well!

Leah Shaffer @leahshaffer.bsky.social · Dec 19

ALL journalists can benefit from the resources and best practices developed by the network of writers who have flourished in science journalism. Science writers and leaders like Siri and Laura help lift unheard voices and share knowledge of diligent reporting. 🧪https://www.theopennotebook.com/

Reposted by John Schneekloth (Jay)

Ingo Hartung @hartungingo.bsky.social · Dec 19

I am about to survive my 1047th week in medicinal chemistry. This editorial is a visit on memory lane. Yes, starting in MedChem initially looks very daunting. MedChems love abbreviations & specialist slang to scare off laymen. But overcoming these hurdles is so rewarding in many dimensions.

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John Schneekloth (Jay) @jschneek.bsky.social · Dec 19

This is the largest RNA we have published on screening to date - over 350 nt in length! This highlights the power of SMMs to discover chemical inhibitors of large, highly complex RNAs. Additionally, mechanistic work shows the mechanism of inhibition to be allosteric! Congrats to all who contributed.

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John Schneekloth (Jay) @jschneek.bsky.social · Dec 19

What a week! Really proud to share this work with Venkat Gopalan and Damien Wilburn in Nucleic Acids Research. We show that our SMM platform can be used to identify allosteric chemical inhibitors of an archaeal RNase P, an ancient ribozyme. academic.oup.com/nar/advance-...

Use of a small molecule microarray screen to identify inhibitors of the catalytic RNA subunit of Methanobrevibacter smithii RNase P

Abstract. Despite interest in developing therapeutics that leverage binding pockets in structured RNAs—whose dysregulation leads to diseases—such drug disc

academic.oup.com

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John Schneekloth (Jay) @jschneek.bsky.social · Dec 19

We hope that this type of approach will eventually have impacts in the study and prediction of large RNA structural ensembles - and perhaps ligand discovery!

John Schneekloth (Jay) @jschneek.bsky.social · Dec 19

Thrilled to see our work in @pnas.org this week! With Pratyush Tiwary, we show that "thermodynamic maps" can be used to infer and predict information about RNA 3D structural ensembles! Proud to have played a small role in this exciting work. www.pnas.org/doi/10.1073/...

www.pnas.org

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John Schneekloth (Jay) @jschneek.bsky.social · Dec 19

This is deeply concerning!

Dr. Ronan Connolly @ronanconnolly.bsky.social · Dec 19

🧪A disturbing trend.

The editor-in-chief of a high profile journal (IF=13.6) was recently offered the opportunity to make up to $250k/year to approve fake papers in his journal ($5k per paper). He declined & reported it. 👍

But, would other editors be tempted? 😬
richardtol.substack.com/p/crime-pays

Crime pays

A paper mill offered me $250,000 per year

richardtol.substack.com

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