Evidence map›Paper›PMID 42427790›Full record

ArticlebioRxiv : the preprint server for biology2026

Cell Penetrating Thyclotides Facilitate Efficient Delivery of Bioactive Peptides into Cells.

Gamze Ayaz, Hongchao Zheng, Harsha Amarasekara, Victor Clausse, Andy Tran, Ferenc Livák, Michael Kruhlak, Daniel H Appella

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. 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

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

8 authors.

Gamze AyazSynthetic Bioactive Molecules Section, Laboratory of Bioorganic Chemistry (LBC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, 8 Center Drive, Room 404, Bethesda, Maryland 20892, United States.
Hongchao ZhengSynthetic Bioactive Molecules Section, Laboratory of Bioorganic Chemistry (LBC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, 8 Center Drive, Room 404, Bethesda, Maryland 20892, United States.
Harsha AmarasekaraSynthetic Bioactive Molecules Section, Laboratory of Bioorganic Chemistry (LBC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, 8 Center Drive, Room 404, Bethesda, Maryland 20892, United States.
Victor ClausseSynthetic Bioactive Molecules Section, Laboratory of Bioorganic Chemistry (LBC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, 8 Center Drive, Room 404, Bethesda, Maryland 20892, United States.
Andy TranMicroscopy Core Facility, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland 20892, United States.
Ferenc LivákLaboratory of Genome Integrity Flow Cytometry Core, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland 20892, United States.
Michael KruhlakMicroscopy Core Facility, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland 20892, United States.
Daniel H AppellaSynthetic Bioactive Molecules Section, Laboratory of Bioorganic Chemistry (LBC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, 8 Center Drive, Room 404, Bethesda, Maryland 20892, United States.

Funding

Chemically Modified Peptide Nucleic AcidsZ01DK031143 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI APPELLA, DANIEL H · 2005 to 2008
$892k
Intramural NIH HHS Z01 DK031143
6 · The paper itself

Abstract

Cell penetrating thyclotides (CPTs) are synthetic molecules that promote highly efficient cellular uptake and endosomal escape of bioactive peptides. While peptides are valuable as medicinal agents, their translation to therapies is often limited by their inability to cross cell membranes. CPTs have a unique combination of chiral tetrahydrofurans and polar sidechains within a molecular scaffold that can be optimized to efficiently deliver peptide cargo into cells. The cellular uptake and endosomal escape of two peptides with anticancer biological activities but low bioavailabilities were remarkably improved after conjugation to a CPT. Using CPTs to overcome barriers to cellular uptake represents a new direction for the intracellular delivery of bioactive molecules, and will accelerate drug development for new medical therapies.

Identifiers

PMID42427790
PMCPMC13345009

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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.