Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry

Jian Fu, Huixiao Fu, Marc Dieu, Iman Halloum, Laurent Kremer, Yufen Xia, Weidong Pan, Stéphane Vincent

Research output: Contribution to specialist publicationArticle

Abstract

In this study, we report a dynamic combinatorial approach along
with highly efficient in situ screening to identify inhibitors of UDPgalactopyranose
mutase (UGM), an essential enzyme involved
in mycobacterial cell wall biosynthesis. These two technologies
converged to the identification of a new UGM inhibitor chemotype.
Importantly, the best molecule not only displayed high affinity for the
target enzyme but also exhibited in vitro growth inhibition against whole
Mycobacterium tuberculosis cells. The strategy described here provides
an avenue to explore a novel inhibitor class for UGMs and paves the way
for further pharmacological studies on tuberculosis treatment.
Original languageEnglish
Pages10632-10635
Number of pages4
Volume53
No.77
Specialist publicationChemical Communications
DOIs
Publication statusPublished - Aug 2017

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Biosynthesis
Cells
Enzymes
Screening
Molecules

Cite this

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abstract = "In this study, we report a dynamic combinatorial approach alongwith highly efficient in situ screening to identify inhibitors of UDPgalactopyranosemutase (UGM), an essential enzyme involvedin mycobacterial cell wall biosynthesis. These two technologiesconverged to the identification of a new UGM inhibitor chemotype.Importantly, the best molecule not only displayed high affinity for thetarget enzyme but also exhibited in vitro growth inhibition against wholeMycobacterium tuberculosis cells. The strategy described here providesan avenue to explore a novel inhibitor class for UGMs and paves the wayfor further pharmacological studies on tuberculosis treatment.",
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Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry. / Fu, Jian; Fu, Huixiao; Dieu, Marc; Halloum, Iman; Kremer, Laurent; Xia, Yufen; Pan, Weidong; Vincent, Stéphane.

In: Chemical Communications, Vol. 53, No. 77, 08.2017, p. 10632-10635.

Research output: Contribution to specialist publicationArticle

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