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Design of a New Peptide Substrate Probe of the Putative Biomarker Legumain with Potential Application in Prostate Cancer Diagnosis ex vivo

Mathur, Sunil; Turnbull, Agnes; Akaev, Iolia; Stevens, Craig; Agrawal, Neerja; Chopra, Mridula; Mincher, David

Authors

Sunil Mathur

Iolia Akaev

Neerja Agrawal

Mridula Chopra



Abstract

The lysosomal endoprotease legumain (asparaginyl endoprotease) has been proposed as a putative biomarker in prostate tumours, in which the enzyme is markedly overexpressed. Overexpression, coupled with highly selective specificity for cleavage of substrates at the C-terminus of asparagine (Asn) residues, make legumain an attractive biochemical target for potential diagnosis, prognosis and treatment. We report the design, synthesis, characterisation and preliminary evaluation of a new rhodamine-B (Rho-B)-labelled legumain peptide substrate probe 5 [Rho-Pro-Ala-Asn-PEG-AQ(4-OH)] and its selective targeting to lysosomes in PC3 prostate cancer cells. Probe 5 was efficiently activated by recombinant human legumain to afford the high quantum yield reporter fluorophore tripeptide 4b (Rho-Pro-Ala-Asn-OH) with concomitant release of intense fluorescence. Furthermore, probe 5 was activated upon incubation with homogenates derived from fresh-frozen tissue material of prostatectomy specimens. Probe 5 represents a new viable biochemical tool for probing the activity of legumain with the potential to be used in ex vivo diagnostics in the cancer pathology laboratory.

Journal Article Type Article
Acceptance Date Dec 9, 2019
Online Publication Date Dec 17, 2019
Publication Date 2020-12
Deposit Date Dec 20, 2019
Publicly Available Date Dec 20, 2019
Print ISSN 1573-3149
Electronic ISSN 1573-3904
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 26
Pages 1965-1980
DOI https://doi.org/10.1007/s10989-019-09994-1
Keywords Prostate cancer, Biomarker, Legumain, Diagnosis, Synthesis
Public URL http://researchrepository.napier.ac.uk/Output/2386672

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Design of a New Peptide Substrate Probe of the Putative Biomarker Legumain with Potential Application in Prostate Cancer Diagnosis Ex Vivo (1.4 Mb)
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
This article is licensed under a Creative Commons Attribution 4.0 International License.







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