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 the...

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Glavni autori: Laurieri, N, Egleton, J, Varney, A, Thinnes, C, Quevedo, C, Seden, P, Thompson, S, Rodrigues-Lima, F, Dairou, J, Dupret, J, Russell, A, Sim, E
Format: Journal article
Jezik:English
Izdano: Public Library of Science 2013
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author Laurieri, N
Egleton, J
Varney, A
Thinnes, C
Quevedo, C
Seden, P
Thompson, S
Rodrigues-Lima, F
Dairou, J
Dupret, J
Russell, A
Sim, E
author_facet Laurieri, N
Egleton, J
Varney, A
Thinnes, C
Quevedo, C
Seden, P
Thompson, S
Rodrigues-Lima, F
Dairou, J
Dupret, J
Russell, A
Sim, E
author_sort Laurieri, N
collection OXFORD
description 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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spelling oxford-uuid:d19d86fc-e8cc-49b8-8d60-6d9c5896184d2022-03-27T07:58:14ZA novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d19d86fc-e8cc-49b8-8d60-6d9c5896184dEnglishSymplectic Elements at OxfordPublic Library of Science2013Laurieri, NEgleton, JVarney, AThinnes, CQuevedo, CSeden, PThompson, SRodrigues-Lima, FDairou, JDupret, JRussell, ASim, EHuman 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.
spellingShingle Laurieri, N
Egleton, J
Varney, A
Thinnes, C
Quevedo, C
Seden, P
Thompson, S
Rodrigues-Lima, F
Dairou, J
Dupret, J
Russell, A
Sim, E
A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
title A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
title_full A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
title_fullStr A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
title_full_unstemmed A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
title_short A novel color change mechanism for breast cancer biomarker detection: naphthoquinones as specific ligands of human arylamine N-acetyltransferase 1
title_sort novel color change mechanism for breast cancer biomarker detection naphthoquinones as specific ligands of human arylamine n acetyltransferase 1
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