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

Résultats de recherche: Contribution à une publication « grand public »Article

Résumé

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.
langueAnglais
Pages10632-10635
Nombre de pages4
Volume53
Non77
Publication spécialiséeChemical Communications
Les DOIs
étatPublié - août 2017

Empreinte digitale

Biosynthesis
Cells
Enzymes
Screening
Molecules

Citer ceci

@misc{6fca99c5c8a14e759749de8b8638c557,
title = "Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry",
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.",
author = "Jian Fu and Huixiao Fu and Marc Dieu and Iman Halloum and Laurent Kremer and Yufen Xia and Weidong Pan and St{\'e}phane Vincent",
year = "2017",
month = "8",
doi = "10.1039/c7cc05251k",
language = "English",
volume = "53",
pages = "10632--10635",
journal = "Chem. Comm.",
issn = "1359-7345",
publisher = "Royal Society of Chemistry",

}

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.

Dans: Chemical Communications, Vol 53, Numéro 77, 08.2017, p. 10632-10635.

Résultats de recherche: Contribution à une publication « grand public »Article

TY - GEN

T1 - Identification of inhibitors targeting Mycobacterium tuberculosis cell wall biosynthesis via dynamic combinatorial chemistry

AU - Fu, Jian

AU - Fu, Huixiao

AU - Dieu, Marc

AU - Halloum, Iman

AU - Kremer, Laurent

AU - Xia, Yufen

AU - Pan, Weidong

AU - Vincent, Stéphane

PY - 2017/8

Y1 - 2017/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85030216065&partnerID=8YFLogxK

U2 - 10.1039/c7cc05251k

DO - 10.1039/c7cc05251k

M3 - Article

VL - 53

SP - 10632

EP - 10635

JO - Chem. Comm.

T2 - Chem. Comm.

JF - Chem. Comm.

SN - 1359-7345

ER -