Evidence map›Paper›PMID 38799658›Full record

ArticleACS central science2024

Nonperturbative Fluorogenic Labeling of Immunophilins Enables the Wash-free Detection of Immunosuppressants.

Marco Bertolini, Lorena Mendive-Tapia, Ouldouz Ghashghaei, Abigail Reese, Charles Lochenie, Anna M Schoepf, Miquel Sintes, Karolina Tokarczyk, Zandile Nare, Andrew D Scott and 5 more

Abstract read
In one paragraph

Article in ACS central science, 2024. 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
–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

8 citing papers in PubMed.

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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

15 authors.

Marco BertoliniCentre for Inflammation Research, The University of Edinburgh, EH16 4UU Edinburgh, U.K.ORCID https://orcid.org/0000-0003-2609-9515
Lorena Mendive-TapiaCentre for Inflammation Research, The University of Edinburgh, EH16 4UU Edinburgh, U.K.
Ouldouz GhashghaeiLaboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences and Institute of Biomedicine UB (IBUB), University of Barcelona, Catalunya, Spain 08007.ORCID https://orcid.org/0000-0002-5524-3697
Abigail ReeseCentre for Inflammation Research, The University of Edinburgh, EH16 4UU Edinburgh, U.K.
Charles LochenieCentre for Inflammation Research, The University of Edinburgh, EH16 4UU Edinburgh, U.K.
Anna M SchoepfLaboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences and Institute of Biomedicine UB (IBUB), University of Barcelona, Catalunya, Spain 08007.
Miquel SintesLaboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences and Institute of Biomedicine UB (IBUB), University of Barcelona, Catalunya, Spain 08007.
Karolina TokarczykConcept Life Sciences Ltd, Edinburgh Bioquarter, Edinburgh EH16 4UX, U.K.
Zandile NareConcept Life Sciences Ltd, Edinburgh Bioquarter, Edinburgh EH16 4UX, U.K.ORCID https://orcid.org/0009-0007-5701-8323
Andrew D ScottConcept Life Sciences Ltd, Edinburgh Bioquarter, Edinburgh EH16 4UX, U.K.
Stephen R KnightRenal Transplant Unit, Queen Elizabeth Hospital, 1345 Govan Road, Glasgow G51 4TF, U.K.
Advait R AithalSchool of Chemistry, University of East Anglia, Norwich NR4 7TJ, U.K.
Amit SachdevaSchool of Chemistry, University of East Anglia, Norwich NR4 7TJ, U.K.ORCID https://orcid.org/0000-0002-3704-5750
Rodolfo LavillaLaboratory of Medicinal Chemistry, Faculty of Pharmacy and Food Sciences and Institute of Biomedicine UB (IBUB), University of Barcelona, Catalunya, Spain 08007.ORCID https://orcid.org/0000-0002-5006-9917
Marc VendrellCentre for Inflammation Research, The University of Edinburgh, EH16 4UU Edinburgh, U.K.ORCID https://orcid.org/0000-0002-5392-9740

Funding

Wellcome Trust
6 · The paper itself

Abstract

Immunosuppressants are clinically approved drugs to treat the potential rejection of transplanted organs and require frequent monitoring due to their narrow therapeutic window. Immunophilins are small proteins that bind immunosuppressants with high affinity, yet there are no examples of fluorogenic immunophilins and their potential application as optical biosensors for immunosuppressive drugs in clinical biosamples. In the present work, we designed novel diazonium BODIPY salts for the site-specific labeling of tyrosine residues in peptides via solid-phase synthesis as well as for late-stage functionalization of whole recombinant proteins. After the optimization of a straightforward one-step labeling procedure for immunophilins PPIA and FKBP12, we demonstrated the application of a fluorogenic analogue of FKBP12 for the selective detection of the immunosuppressant drug tacrolimus, including experiments in urine samples from patients with functioning renal transplants. This chemical methodology opens new avenues to rationally design wash-free immunophilin-based biosensors for rapid therapeutic drug monitoring.

Identifiers

PMID38799658
PMCPMC11117681

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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.