Evidence map›Paper›PMID 26791894›Full record

ArticleNature chemistry2016

Π-Clamp-mediated cysteine conjugation.

Chi Zhang, Matthew Welborn, Tianyu Zhu, Nicole J Yang, Michael S Santos, Troy Van Voorhis, Bradley L Pentelute

Open access · bronzeAbstract read
In one paragraph

Article in Nature chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
14.1field-weighted citation impact, top 1% of its field
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

129 citing papers in PubMed, 287 citations in OpenAlex.

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  14. A Chemically Induced CRISPR/dCas13Journal of medicinal chemistry · 2025
    Article
  15. Article
  16. Peptide Tags for Site-Selective Nonenzymatic Covalent Modification of Proteins.Journal of peptide science : an official publication of the European Peptide Society · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. Orthogonal Site-Specific Dual Bioconjugation of Aryl and Alkyl Thiols.Journal of the American Chemical Society · 2025
    Article

69 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Chi ZhangDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Matthew WelbornDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Tianyu ZhuDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Nicole J YangDepartment of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Michael S SantosDepartment of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Troy Van VoorhisDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Bradley L PenteluteDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Massachusetts Institute of Technology · US

Funding

TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
Cysteine ArylationR01GM110535 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI PENTELUTE, BRADLEY LETHER · 2014 to 2018
$1.5M
Acquisition of Octet Biolayer Interferometry system for MIT biophysics facilityS10OD016326 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IMPERIALI, BARBARA · 2014 to 2014
$180k
NIEHS NIH HHS P30 ES002109NIEHS NIH HHS P30-ES002109NIGMS NIH HHS R01 GM110535NIGMS NIH HHS R01GM110535NIH HHS S10 OD016326
6 · The paper itself

Abstract

Site-selective functionalization of complex molecules is one of the most significant challenges in chemistry. Typically, protecting groups or catalysts must be used to enable the selective modification of one site among many that are similarly reactive, and general strategies that selectively tune the local chemical environment around a target site are rare. Here, we show a four-amino-acid sequence (Phe-Cys-Pro-Phe), which we call the 'π-clamp', that tunes the reactivity of its cysteine thiol for site-selective conjugation with perfluoroaromatic reagents. We use the π-clamp to selectively modify one cysteine site in proteins containing multiple endogenous cysteine residues. These examples include antibodies and cysteine-based enzymes that would be difficult to modify selectively using standard cysteine-based methods. Antibodies modified using the π-clamp retained binding affinity to their targets, enabling the synthesis of site-specific antibody-drug conjugates for selective killing of HER2-positive breast cancer cells. The π-clamp is an unexpected approach to mediate site-selective chemistry and provides new avenues to modify biomolecules for research and therapeutics.

Indexed as

Biological PhenomenaCatalysisCysteineHumansProteinsCysteineProteins

Identifiers

PMID26791894
PMCPMC4861612
OpenAlexW2258806502

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.