Evidence map›Paper›PMID 35039490›Full record

ArticleNature communications2022

Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction.

Md Shafiqul Islam, Samuel L Junod, Si Zhang, Zakey Yusuf Buuh, Yifu Guan, Mi Zhao, Kishan H Kaneria, Parmila Kafley, Carson Cohen, Robert Maloney and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Fluorine-Thiol Displacement Stapling on the Disordered αSynlett : accounts and rapid communications in synthetic organic chemistry · 2025
    Article
  7. Review
  8. Review
  9. Peptide macrocyclisationChemical science · 2024
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
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

14 authors at 1 institution in 1 country.

Md Shafiqul IslamDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Samuel L JunodDepartment of Biology, Temple University, 1900 N. 12th Street, Philadelphia, PA, 19122, USA.
Si ZhangDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Zakey Yusuf BuuhDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Yifu GuanDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Mi ZhaoDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Kishan H KaneriaDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Parmila KafleyDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Carson CohenDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Robert MaloneyDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Zhigang LyuDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Vincent A VoelzDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
Weidong YangDepartment of Biology, Temple University, 1900 N. 12th Street, Philadelphia, PA, 19122, USA.
Rongsheng E WangDepartment of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA. rosswang@temple.edu.ORCID http://orcid.org/0000-0002-5749-7447
Temple University · US

Funding

Super-resolution Microscopy Study of Molecular Transport MechanismsR35GM122552 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI Weidong Yang · 2017 to 2026
$4.5M
Markov State Model approaches for folding, binding and designR01GM123296 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI VOELZ, VINCENT · 2017 to 2025
$3.1M
Steric-free labeling strategies to study disease-related non-histone substrates of post-translational modificationsR35GM133468 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI Ross Wang · 2019 to 2026
$2.9M
Structure and Function of the Ciliary Pore ComplexR01GM116204 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VERHEY, KRISTEN J., YANG, WEIDONG · 2015 to 2018
$2.1M
Computer Cluster for Computational Biology and BiophysicsS10OD020095 · OD · TEMPLE UNIV OF THE COMMONWEALTH · PI LEVY, RONALD · 2015 to 2015
$442k
NIGMS NIH HHS R01 GM116204NIGMS NIH HHS R01 GM123296NIGMS NIH HHS R35 GM122552NIGMS NIH HHS R35 GM133468NIH HHS S10 OD020095
6 · The paper itself

Abstract

We report the discovery of a facile peptide macrocyclization and stapling strategy based on a fluorine thiol displacement reaction (FTDR), which renders a class of peptide analogues with enhanced stability, affinity, cellular uptake, and inhibition of cancer cells. This approach enabled selective modification of the orthogonal fluoroacetamide side chains in unprotected peptides in the presence of intrinsic cysteines. The identified benzenedimethanethiol linker greatly promoted the alpha helicity of a variety of peptide substrates, as corroborated by molecular dynamics simulations. The cellular uptake of benzenedimethanethiol stapled peptides appeared to be universally enhanced compared to the classic ring-closing metathesis (RCM) stapled peptides. Pilot mechanism studies suggested that the uptake of FTDR-stapled peptides may involve multiple endocytosis pathways in a distinct pattern in comparison to peptides stapled by RCM. Consistent with the improved cell permeability, the FTDR-stapled lead Axin and p53 peptide analogues demonstrated enhanced inhibition of cancer cells over the RCM-stapled analogues and the unstapled peptides.

Indexed as

Amino Acid SequenceAxin ProteinCell Membrane PermeabilityCell-Penetrating PeptidesCross-Linking ReagentsCyclizationFluorineHEK293 CellsHumansMacrocyclic CompoundsMagnetic Resonance SpectroscopyModels, MolecularMolecular Dynamics SimulationPeptidesSulfhydryl CompoundsThermodynamicsAxin ProteinCell-Penetrating PeptidesCross-Linking ReagentsFluorineMacrocyclic CompoundsPeptidesSulfhydryl CompoundsTumor Suppressor Protein p53

Identifiers

PMID35039490
PMCPMC8763920
OpenAlexW4225767184

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.