Evidence map›Paper›PMID 40841495›Full record

ArticleNature chemical biology2025

Site-selective protein editing by backbone extension acyl rearrangements.

Leah T Roe, Isabel M Piper, Carly K Schissel, Taylor L Dover, Bhavana Shah, Noah X Hamlish, Arjun M Garapaty, Shuai Zheng, Diondra A Dilworth, Nicole Wong and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Chemical Biology 2025: Highlights From the Ch/Bi145 Course at Caltech.Chembiochem : a European journal of chemical biology · 2026
    Review
  2. Review
  3. Article
  4. Co-Translational Incorporation ofJournal of the American Chemical Society · 2026
    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

15 authors.

Leah T RoeDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2487-5587
Isabel M PiperDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Carly K SchisselDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-0773-5168
Taylor L DoverDepartment of Chemistry, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2358-0488
Bhavana ShahProcess Development, Attribute Sciences, Amgen, Inc., Thousand Oaks, CA, USA.
Noah X HamlishDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Arjun M GarapatyDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0004-5483-8703
Shuai ZhengDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-9085-4410
Diondra A DilworthDepartment of Chemistry, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0009-0004-3870-0237
Nicole WongDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Zhongqi ZhangProcess Development, Attribute Sciences, Amgen, Inc., Thousand Oaks, CA, USA.ORCID http://orcid.org/0000-0002-8326-6714
Abhishek ChatterjeeDepartment of Chemistry, Boston College, Chestnut Hill, MA, USA.ORCID http://orcid.org/0000-0002-6231-5302
Matthew B FrancisDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA. mfrancis@berkeley.edu.ORCID http://orcid.org/0000-0003-2837-2538
Scott J MillerDepartment of Chemistry, Yale University, New Haven, CT, USA. scott.miller@yale.edu.ORCID http://orcid.org/0000-0001-7817-1318
Alanna SchepartzDepartment of Chemistry, University of California, Berkeley, Berkeley, CA, USA. schepartz@berkeley.edu.ORCID http://orcid.org/0000-0003-2127-3932

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protein and polypeptide heteropolymers containing non-α-backbone monomers are highly desirable as potential materials and therapeutics but many remain difficult or impossible to biosynthesize in cells using traditional genetic code expansion. Here we describe a next-generation approach to such materials that relies instead on proximity-guided intramolecular rearrangements that edit the protein backbone post-translationally. This approach relies on orthogonal aminoacyl-tRNA synthetase enzymes that accept α-hydroxy acid monomers whose side chains contain masked nucleophiles. Introduction of such an α-hydroxy acid into a protein translated in vivo, followed by nucleophile unmasking, sets up a thermodynamically favored intramolecular backbone extension acyl rearrangement (BEAR) reaction that edits the protein to install an extended-backbone monomer. In the examples described here, BEAR reactions are used to generate protein heteropolymers containing a β-backbone, γ-backbone or δ-backbone. This report represents a general strategy to install extended backbones into genetically encoded proteins and peptides expressed in cells.

Indexed as

Amino Acyl-tRNA SynthetasesProtein EngineeringProteinsPeptidesProtein Processing, Post-TranslationalAmino Acyl-tRNA SynthetasesPeptidesProteins

Identifiers

PMID40841495

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.