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@ARTICLE{Benltifa:90093,
author = {Benltifa, M. and Hayes, J. M. and Vidal, S. and Gueyrard,
D. and Goekjian, P. G. and Praly, J.-P. and Kizilis, G. and
Tiraidis, C. and Alexacou, K.-M. and Chrysina, E. D. and
Zographos, S. E. and Leonidas, D. D. and Archontis, G. and
Oikonomakos, N. G. and DESY},
title = {{G}lucose-based spiro-isoxazolines: {A} new family of
potent glycogen phosphorylase inhibitors},
journal = {Bioorganic $\&$ medicinal chemistry},
volume = {17},
issn = {0968-0896},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {PHPPUBDB-11918},
pages = {7368-7380},
year = {2009},
note = {© Elsevier Ltd.},
abstract = {A series of glucopyranosylidene-spiro-isoxazolines was
prepared through regio- and stereoselective
[3+2]-cycloaddition between the methylene acetylated
exo-glucal and aromatic nitrile oxides. The deprotected
cycloadducts were evaluated as inhibitors of muscle glycogen
phosphorylase b. The carbohydrate-based family of five
inhibitors displays K(i) values ranging from 0.63 to 92.5
microM. The X-ray structures of the enzyme-ligand complexes
show that the inhibitors bind preferentially at the
catalytic site of the enzyme retaining the less active
T-state conformation. Docking calculations with GLIDE in
extra-precision (XP) mode yielded excellent agreement with
experiment, as judged by comparison of the predicted binding
modes of the five ligands with the crystallographic
conformations and the good correlation between the docking
scores and the experimental free binding energies. Use of
docking constraints on the well-defined positions of the
glucopyranose moiety in the catalytic site and redocking of
GLIDE-XP poses using electrostatic potential fit-determined
ligand partial charges in quantum polarized ligand docking
(QPLD) produced the best results in this regard.},
keywords = {Crystallography, X-Ray / Enzyme Inhibitors: chemistry /
Enzyme Inhibitors: pharmacology / Glucose: chemistry /
Glycogen Phosphorylase: antagonists $\&$ inhibitors /
Glycogen Phosphorylase: metabolism / Kinetics / Magnetic
Resonance Spectroscopy / Models, Molecular / Oxazoles:
chemistry / Oxazoles: pharmacology / Spectrometry, Mass,
Electrospray Ionization / Enzyme Inhibitors (NLM Chemicals)
/ Oxazoles (NLM Chemicals) / Glucose (NLM Chemicals) /
Glycogen Phosphorylase (NLM Chemicals)},
cin = {EMBL(-2012)},
ddc = {540},
cid = {$I:(DE-H253)EMBL_-2012_-20130307$},
pnm = {FS Beamline without reference (POF1-550) / DORIS Beamline
K1.1 (POF1-550)},
pid = {G:(DE-H253)POF1-No-Ref-20130405 /
G:(DE-H253)POF1-K1.1-20130405},
experiment = {EXP:(DE-H253)Unknown-BL-20150101 /
EXP:(DE-H253)D-K1.1-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:19781947},
UT = {WOS:000270434000031},
doi = {10.1016/j.bmc.2009.08.060},
url = {https://bib-pubdb1.desy.de/record/90093},
}