Evidence map›Paper›PMID 32315152›Full record

ArticleACS chemical biology2020

Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold.

Huawu Yin, Yen-Hua Huang, Kirsten Deprey, Nicholas D Condon, Joshua A Kritzer, David J Craik, Conan K Wang

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 20 citations in OpenAlex.

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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

7 authors at 2 institutions in 2 countries.

Huawu YinInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Yen-Hua HuangInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0001-6937-2660
Kirsten DepreyDepartment of Chemistry, Tufts University, Medford, Massachusetts 02155, United States.
Nicholas D CondonInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0002-1833-1129
Joshua A KritzerDepartment of Chemistry, Tufts University, Medford, Massachusetts 02155, United States.ORCID 0000-0003-2878-6781
David J CraikInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0003-0007-6796
Conan K WangInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0002-7973-7632
The University of Queensland · AUTufts University · US

Funding

Cell Penetration Profiling for BiotherapeuticsR01GM127585 · NIGMS · TUFTS UNIVERSITY MEDFORD · PI KRITZER, JOSHUA A · 2018 to 2022
$1.6M
NIGMS NIH HHS R01 GM127585
6 · The paper itself

Abstract

Cyclotides are macrocyclic peptides with exceptionally stable structures and have been reported to penetrate cells, making them promising scaffolds for the delivery of inhibitory peptides to target intracellular proteins. However, their cellular uptake and cytosolic localization have been poorly understood until now, which has limited their therapeutic potential. In this study, the recently developed chloroalkane penetration assay was combined with established assays to characterize the cellular uptake and cytosolic delivery of the prototypic cyclotide, kalata B1. We show that kalata B1 enters the cytosol at low efficiency. A structure-activity study of residues in loop 6 showed that some modifications, such as increasing cationic residue content, did not affect delivery efficiency, whereas others, including introducing a single hydrophobic amino acid, did significantly improve cytosolic delivery. Our results provide a foundation for the further development of a structurally unique class of scaffolds for the delivery of therapeutic cargoes into cells.

Indexed as

Amino Acid SequenceCyclotidesCystineCytosolFluorescent DyesHeLa CellsHumansMicroscopy, ConfocalMolecular StructureCyclotidesCystineFluorescent Dyeskalata B1

Identifiers

PMID32315152
PMCPMC7831380
OpenAlexW3016520204

What OpenQuestion holds

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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.