Evidence map›Paper›PMID 38819260›Full record

ArticleJournal of the American Chemical Society2024

Genetically Encoded Epoxide Warhead for Precise and Versatile Covalent Targeting of Proteins.

Jinpeng Zhang, Xia Wang, Qingjun Huang, Jinsong Ye, Jie Wang

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. ERK autoinhibition mechanism informs a drug combination strategy.Protein science : a publication of the Protein Society · 2026
    Article
  2. Article
  3. Review
  4. Proteome-Wide Covalent Targeting of Acidic Residues with TunableJournal of the American Chemical Society · 2025
    Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Jinpeng ZhangDepartment of Chemistry, Research Center for Chemical Biology and Omics Analysis, College of Science, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
Xia WangDepartment of Chemistry, Research Center for Chemical Biology and Omics Analysis, College of Science, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
Qingjun HuangDepartment of Chemistry, Research Center for Chemical Biology and Omics Analysis, College of Science, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
Jinsong YeDepartment of Chemistry, Research Center for Chemical Biology and Omics Analysis, College of Science, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
Jie WangDepartment of Chemistry, Research Center for Chemical Biology and Omics Analysis, College of Science, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.ORCID 0000-0001-7602-5050

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genetically encoding a proximal reactive warhead into the protein binder/drug has emerged as an efficient strategy for covalently binding to protein targets, enabling broad applications. To expand the reactivity scope for targeting the diverse natural residues under physiological conditions, the development of a genetically encoded reactive warhead with excellent stability and broad reactivity is highly desired. Herein, we reported the genetic encoding of epoxide-containing tyrosine (EPOY) for developing covalent protein drugs. Our study demonstrates that EPOY, when incorporated into a nanobody (KN035), can cross-link with different side chains (mutations) at the same position of PD-L1 protein. Significantly, a single genetically encoded reactive warhead that is capable of covalent and site-specific targeting to 10 different nucleophilic residues was achieved for the first time. This would largely expand the scope of covalent warhead and inspire the development of covalent warheads for both small-molecule drugs and protein drugs. Furthermore, we incorporate the EPOY into a designed ankyrin repeat protein (Darpin

Indexed as

Epoxy CompoundsB7-H1 AntigenHumansProto-Oncogene Proteins p21(ras)Single-Domain AntibodiesTyrosineB7-H1 AntigenCD274 protein, humanEpoxy CompoundsKRAS protein, humanProto-Oncogene Proteins p21(ras)Single-Domain AntibodiesTyrosine

Identifiers

PMID38819260
PMCPMC11177858

What OpenQuestion holds

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Registered trials

None linked

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.