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Monitoring of the ethionamide pro-drug activation in mycobacteria by (1)H high resolution magic angle spinning NMR.

Abstract：

:In this study, we use HRMAS NMR as a non-invasive technique to monitor the in vivo metabolism of a xenobiotic. The antituberculosis Ethionamide is a pro-drug that has to be activated in mycobacteria before inhibiting its cellular target. The use of (1)H HRMAS NMR has allowed to detect a metabolite (ETH*) of the drug directly in living bacteria, even with a spectrometer operating at the relatively low magnetic field of 300MHz. We show that metabolism monitoring of an unlabelled drug at a therapeutically relevant concentration as low as 5mug/ml is within reach of the technique. (1)H HRMAS NMR in combination with diffusion filtering leads to the conclusion that the metabolite is located inside the intact cells. The comparison of the metabolite NMR signature with that of synthetic molecules proves the non-identity of ETH* with the ETH derivatives described previously in the literature.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hanoulle X,Wieruszeski JM,Rousselot-Pailley P,Landrieu I,Baulard AR,Lippens G

doi

10.1016/j.bbrc.2005.03.197

subject

Has Abstract

pub_date

2005-06-03 00:00:00

pages

452-8

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)00639-X

journal_volume

331

pub_type

杂志文章

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