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Steven Cheng

@scheng23.bsky.social

535 followers 1.2K following 36 posts

Chemistry & Chemical Biology PhD Candidate @Harvard woolab.org | Chemical Engineering @Stanford Alumnus | Small molecules 💊, PTMs (esp O-GlcNAc 🟦), RNA splicing 🧬

Posts Replies Media

Steven Cheng @scheng23.bsky.social · 07/04/2025

Therapeutic potential of allosteric HECT E3 ligase inhibition www.cell.com/cell/fulltex... "we discover inhibitors that bind a cryptic cavity distant from the catalytic cysteine" ... "these inhibitors restrict an essential catalytic motion by extending an α helix over a conserved glycine hinge"

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Steven Cheng @scheng23.bsky.social · 21/03/2025

Very interesting screening approach leveraging different technologies including DELs, photocleavable linkers, microfluidics, RNA-seq to discover new bioactive VHL molecular glues

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Steven Cheng @scheng23.bsky.social · 21/03/2025

www.nature.com/articles/s41... www.nature.com/articles/d41... A polyene macrolide targeting phospholipids in the fungal cell membrane New antifungal breaks the mould "Mandimycin is an antifungal molecule that acts by specifically targeting phospholipids"

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Steven Cheng @scheng23.bsky.social · 10/01/2025

"On a molecular level, our structural studies reveal that interdictors bind in a linkerless heterobifunctional manner to both the rRNA and the nascent peptide chain ... much the way a PROTAC can be modularly designed and constructed"

Figure 3. (A) Representative cryo-EM map of a stalled RNC with a tRNA in the P site, bound to IDB-001.
Inset shows a closeup of the PTC containing the IDB-001 (yellow), P-site tRNA (green), nascent
chain (salmon), rRNA (dark blue), and signal for ions and water molecules (red).

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Steven Cheng @scheng23.bsky.social · 13/12/2024

TIL there's an E3 ligase named "itchy"

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Steven Cheng @scheng23.bsky.social · 11/12/2024

www.nature.com/articles/s41... Aromatic ring-opening metathesis 🤨

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Steven Cheng @scheng23.bsky.social · 01/12/2024

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Steven Cheng @scheng23.bsky.social · 21/11/2024

www.pnas.org/doi/10.1073/... Targeted degradation of Pin1 by protein-destabilizing compounds “Molecular crowbar” degraders, will be interesting to see generalizability to other targets (BRD4 🫥)

Cartoon schematic of molecular crowbar degraders. Caption: Schematic illustration of the proposed mechanism of how a molecular crowbar induces Pin1 degradation. Binding of our agents to Pin1 brings the reactive acetyl group of the inhibitor close to Cys113. Upon formation of a covalent bond between the inhibitor to Cys113, the inhibitor-bound Cys113 acts like a molecular crowbar. It destabilizes the short helix D causing the helix to unfold and loop FG to move its position exposing hydrophobic residues such as Trp 73. Hence, our inhibitor acts as a molecular crowbar that opens up and destabilizes Pin and subsequent cellular degradation.

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