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A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1

A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
Human arylamine N-acetyltransferase 1 (hNAT1) has become an attractive potential biomarker for estrogen-receptor-positive breast cancers. We describe here the mechanism of action of a selective non-covalent colorimetric biosensor for the recognition of hNAT1 and its murine homologue, mNat2, over their respective isoenzymes, leading to new opportunities in diagnosis. On interaction with the enzyme, the naphthoquinone probe undergoes an instantaneous and striking visible color change from red to blue. Spectroscopic, chemical, molecular modelling and biochemical studies reported here show that the color change is mediated by selective recognition between the conjugate base of the sulfonamide group within the probe and the conjugate acid of the arginine residue within the active site of both hNAT1 and mNat2. This represents a new mechanism for selective biomarker sensing and may be exploited as a general approach to the specific detection of biomarkers in disease.
1932-6203
1-6
Aziz, Syed A.
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Laurieri, Nicola
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Egleton, James E.
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Varney, Amy
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Thinnes, Cyrille C.
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Quevedo, Camilo E.
35582bce-4f8c-4093-befc-3774ade08a43
Seden, Peter T.
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Thompson, Sam
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Rodrigues-Lima, Fernando
2006f056-5fb8-438c-9b38-5030f31a20e4
Dairou, Julien
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Dupret, Jean-Marie
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Russell, Angela J.
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Sim, Edith
76b9b428-c005-44d0-972d-edbf3b169443
Aziz, Syed A.
b05b2615-a716-40e1-abbb-184db4a399ee
Laurieri, Nicola
83aa6a45-b081-4cb4-88ed-eee80ffb967c
Egleton, James E.
b6e7e09f-90e4-42c9-8123-34b3eb6448eb
Varney, Amy
f2abc8bf-7b6d-43b5-b92b-20113be5ac18
Thinnes, Cyrille C.
3bfbbf02-e6b6-4935-af0d-f30ce487d0bd
Quevedo, Camilo E.
35582bce-4f8c-4093-befc-3774ade08a43
Seden, Peter T.
4dd1082b-132c-4199-98f4-278b1aa06cb4
Thompson, Sam
99b7e34e-fe24-401c-b7b0-64e56cbbbcb1
Rodrigues-Lima, Fernando
2006f056-5fb8-438c-9b38-5030f31a20e4
Dairou, Julien
b74c4fec-4a11-4262-a45b-9fc6d3ecf14b
Dupret, Jean-Marie
1bb48ae0-59d4-451f-9048-41f67d3cbd75
Russell, Angela J.
da250fde-2cb6-4f3f-971b-a9a66678e1d3
Sim, Edith
76b9b428-c005-44d0-972d-edbf3b169443

Aziz, Syed A., Laurieri, Nicola, Egleton, James E., Varney, Amy, Thinnes, Cyrille C., Quevedo, Camilo E., Seden, Peter T., Thompson, Sam, Rodrigues-Lima, Fernando, Dairou, Julien, Dupret, Jean-Marie, Russell, Angela J. and Sim, Edith (2013) A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1. PLoS ONE, 8 (8), 1-6. (doi:10.1371/journal.pone.0070600).

Record type: Article

Abstract

Human arylamine N-acetyltransferase 1 (hNAT1) has become an attractive potential biomarker for estrogen-receptor-positive breast cancers. We describe here the mechanism of action of a selective non-covalent colorimetric biosensor for the recognition of hNAT1 and its murine homologue, mNat2, over their respective isoenzymes, leading to new opportunities in diagnosis. On interaction with the enzyme, the naphthoquinone probe undergoes an instantaneous and striking visible color change from red to blue. Spectroscopic, chemical, molecular modelling and biochemical studies reported here show that the color change is mediated by selective recognition between the conjugate base of the sulfonamide group within the probe and the conjugate acid of the arginine residue within the active site of both hNAT1 and mNat2. This represents a new mechanism for selective biomarker sensing and may be exploited as a general approach to the specific detection of biomarkers in disease.

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Accepted/In Press date: 30 May 2013
Published date: 5 August 2013
Organisations: Chemistry

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Local EPrints ID: 403604
URI: https://eprints.soton.ac.uk/id/eprint/403604
ISSN: 1932-6203
PURE UUID: a83cdc3c-f47f-4100-a3b6-4e9b11bbb3dc
ORCID for Sam Thompson: ORCID iD orcid.org/0000-0001-6267-5693

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Date deposited: 07 Dec 2016 11:33
Last modified: 07 Aug 2019 00:29

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Contributors

Author: Syed A. Aziz
Author: Nicola Laurieri
Author: James E. Egleton
Author: Amy Varney
Author: Cyrille C. Thinnes
Author: Camilo E. Quevedo
Author: Peter T. Seden
Author: Sam Thompson ORCID iD
Author: Fernando Rodrigues-Lima
Author: Julien Dairou
Author: Jean-Marie Dupret
Author: Angela J. Russell
Author: Edith Sim

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