Evidence map›Paper›PMID 38464067›Full record

ArticlebioRxiv : the preprint server for biology2024

Chemical tools to expand the ligandable proteome: diversity-oriented synthesis-based photoreactive stereoprobes.

Daisuke Ogasawara, David B Konrad, Zher Yin Tan, Kimberly L Carey, Jessica Luo, Sang Joon Won, Haoxin Li, Trever Carter, Kristen E DeMeester, Evert Njomen and 4 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Daisuke Ogasawara
David B Konrad
Zher Yin Tan
Kimberly L Carey
Jessica Luo
Sang Joon Won
Haoxin Li
Trever Carter
Kristen E DeMeester
Evert Njomen
Stuart L Schreiber
Ramnik J Xavier
Bruno Melillo
Benjamin F Cravatt

Funding

RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteinsU19AI142784 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI SHILOH, MICHAEL · 2019 to 2023
$36.9M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Chemical Proteomic Platforms for Radically Expanding Cancer DruggabilityR35CA231991 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BENJAMIN F CRAVATT · 2018 to 2026
$9.5M
NCI NIH HHS R35 CA231991NIAID NIH HHS U19 AI142784NIDDK NIH HHS P30 DK043351
6 · The paper itself

Abstract

Chemical proteomics enables the global assessment of small molecule-protein interactions in native biological systems and has emerged as a versatile approach for ligand discovery. The range of small molecules explored by chemical proteomics has, however, been limited. Here, we describe a diversity-oriented synthesis (DOS)-inspired library of stereochemically-defined compounds bearing diazirine and alkyne units for UV light-induced covalent modification and click chemistry enrichment of interacting proteins, respectively. We find that these 'photo-stereoprobes' interact in a stereoselective manner with hundreds of proteins from various structural and functional classes in human cells and demonstrate that these interactions can form the basis for high-throughput screening-compatible nanoBRET assays. Integrated phenotypic analysis and chemical proteomics identified photo-stereoprobes that modulate autophagy by engaging the mitochondrial serine protease CLPP. Our findings show the utility of photo-stereoprobes for expanding the ligandable proteome, furnishing target engagement assays, and discovering and characterizing bioactive small molecules by cell-based screening.

Identifiers

PMID38464067
PMCPMC10925180

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.