Evidence map›Paper›PMID 32589815›Full record

ArticleAngewandte Chemie (International ed. in English)2020

Design of Optical-Imaging Probes by Screening of Diverse Substrate Libraries Directly in Disease-Tissue Extracts.

Martina Tholen, Joshua J Yim, Katarzyna Groborz, Euna Yoo, Brock A Martin, Nynke S van den Berg, Marcin Drag, Matthew Bogyo

Abstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2020. 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
–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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Non-Canonical Amino Acids in Analyses of Protease Structure and Function.International journal of molecular sciences · 2023
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Massively parallel, computationally guided design of a proenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. 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

8 authors.

Martina TholenDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Joshua J YimDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Katarzyna GroborzDepartment of Chemical Biology and Bioimaging, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.
Euna YooDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Brock A MartinDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Nynke S van den BergDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA, 94305, USA.
Marcin DragDepartment of Chemical Biology and Bioimaging, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.
Matthew BogyoDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.ORCID 0000-0003-3753-4412

Funding

Dual orthogonal fluorescent protease sensors for image guided surgeryR01EB028628 · NIBIB · STANFORD UNIVERSITY · PI BOGYO, MATTHEW · 2019 to 2023
$1.9M
Generation of highly selective activity based probes using chemically modified phageR01EB026285 · NIBIB · STANFORD UNIVERSITY · PI BOGYO, MATTHEW · 2018 to 2021
$1.9M
NIBIB NIH HHS R01 EB026285NIBIB NIH HHS R01 EB028628
6 · The paper itself

Abstract

Fluorescently quenched probes that are specifically activated in the cancer microenvironment have great potential application for diagnosis, early detection, and surgical guidance. These probes are often designed to target specific enzymes associated with diseases by direct optimization using single purified enzymes. However, this can result in painstaking chemistry efforts to produce a probe with suboptimal performance when applied in vivo. We describe here an alternate, unbiased activity-profiling approach in which whole tissue extracts are used to directly identify optimal peptide sequences for probe design. Screening of tumor extracts with a hybrid combinatorial substrate library (HyCoSuL) identified a combination of natural and non-natural amino-acid residues that was used to generate highly efficient tumor-specific probes. This new strategy simplifies and enhances the process of probe optimization without any a priori knowledge of enzyme targets and has the potential to be applied to diverse disease states using clinical or animal-model tissue samples.

Indexed as

AnimalsCombinatorial Chemistry TechniquesFluorescent DyesHeterograftsHumansMiceOptical ImagingProteolysisReproducibility of ResultsSubstrate SpecificityTissue ExtractsTumor MicroenvironmentFluorescent DyesTissue Extractsdisease tissuein-vivo imagingprobe designprotease profiling

Identifiers

PMID32589815
PMCPMC8163102

What OpenQuestion holds

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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.