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@ARTICLE{Bouckaert:168260,
author = {Bouckaert, Julie and Li, Zhaoli and Xavier, Catarina and
Almant, Mehdi and Caveliers, Vicky and Lahoutte, Tony and
Weeks, Stephen and Kovensky, José and Gouin, Sébastien G.},
title = {{H}eptyl α- {D} -{M}annosides {G}rafted on a
β-{C}yclodextrin {C}ore {T}o {I}nterfere with {E}scherichia
coli {A}dhesion: {A}n {I}n {V}ivo {M}ultivalent {E}ffect},
journal = {Chemistry},
volume = {19},
number = {24},
issn = {0947-6539},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DESY-2014-02452},
pages = {7847 - 7855},
year = {2013},
note = {© WILEY‐VCH Verlag GmbH $\&$ Co. KGaA, Weinheim},
abstract = {n‐Heptyl α‐D‐mannoside (HM) has previously been
identified as a nanomolar FimH antagonist able to prevent
Escherichia coli adhesion. We have designed mono‐ and
heptavalent glycoconjugates in which HM is tethered to
β‐cyclodextrin (β‐CD) through short and long spacers.
One‐pot click or co‐clicking procedures were developed
to directly obtain the glycoconjugates from unprotected HM
and β‐CD precursors. These FimH antagonists were examined
biophysically and in vivo. Reverse titrations by isothermal
calorimetry led to trapping of the short‐tethered
heptavalent β‐CD in a complex with three FimH lectins.
Combined dynamic light scattering and small‐angle X‐ray
solution scattering data allowed the construction of a model
of the FimH trimer. The heptavalent β‐CDs were shown to
capture and aggregate living bacteria in solution and are
therefore also able to aggregate FimH when attached to
different bacteria pili. The first in vivo evaluation of
multivalent FimH inhibitors has been performed. The
heptavalent β‐CDs proved to be much more effective
anti‐adhesive agents than monovalent references with doses
of around 2 μg instilled in the mouse bladder leading to
a significantly decreased E. coli load. Intravenously
injected radiolabeled glycoconjugates can rapidly reach the
mouse bladder and >2 μg concentrations can easily be
retained over 24 h to prevent fluxing bacteria from
rebinding.},
cin = {EMBL-User},
ddc = {540},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {FS Beamline without reference (POF2-544)},
pid = {G:(DE-H253)POF2-No-Ref-20130405},
experiment = {EXP:(DE-H253)Unknown-BL-20150101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000319825500025},
pubmed = {pmid:23595913},
doi = {10.1002/chem.201204015},
url = {https://bib-pubdb1.desy.de/record/168260},
}