Journal of Medicinal Chemistry
Article
(
10) Jin, R. S.; Banke, T. G.; Mayer, M. L.; Traynelis, S. F.; Gouaux,
domain in complex with agonists, antagonists and allosteric
modulators. Neuropharmacology 2011, 60, 135−50.
E. Structural basis for partial agonist action at ionotropic glutamate
receptors. Nat. Neurosci. 2003, 6, 803−810.
(26) Coquelle, T.; Christensen, J. K.; Banke, T. G.; Madsen, U.;
Schousboe, A.; Pickering, D. S. Agonist discrimination between AMPA
receptor subtypes. NeuroReport 2000, 11, 2643−2648.
(27) Honore, T.; Nielsen, M. Complex structure of quisqualate-
sensitive glutamate receptors in rat cortex. Neurosci. Lett. 1985, 54,
27−32.
(
11) Frandsen, A.; Pickering, D. S.; Vestergaard, B.; Kasper, C.;
Nielsen, B. B.; Greenwood, J. R.; Campiani, G.; Fattorusso, C.;
Gajhede, M.; Schousboe, A.; Kastrup, J. S. Tyr702 is an important
determinant of agonist binding and domain closure of the ligand-
binding core of GluR2. Mol. Pharmacol. 2005, 67, 703−713.
3
(
12) Fenwick, M. K.; Oswald, R. E. NMR spectroscopy of the ligand
(28) Braitman, D. J.; Coyle, J. T. Inhibition of [ H]kainic acid
binding core of ionotropic glutamate receptor 2 bound to 5-
receptor binding by divalent cations correlates with ion affinity for the
calcium channel. Neuropharmacology 1987, 26, 1247−1251.
substituted willardiine partial agonists. J. Mol. Biol. 2008, 378, 673−
685.
(29) Sills, M. A.; Fagg, G.; Pozza, M.; Angst, C.; Brundish, D. E.;
3
(
13) Fenwick, M. K.; Oswald, R. E. On the mechanisms of α-amino-
-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor bind-
ing to glutamate and kainate. J. Biol. Chem. 2010, 285, 12334−12343.
14) Ahmed, A. H.; Ptak, C. P.; Fenwick, M. K.; Hsieh, C.-L.;
Hurt, S. D.; Wilusz, E. J.; Williams, M. [ H]CGP 39653: a new N-
3
methyl-D-aspartate antagonist radioligand with low nanomolar affinity
in rat brain. Eur. J. Pharmacol. 1991, 192, 19−24.
̇
(30) Assaf, Z.; Larsen, A. P.; Venskutonyte, R.; Han, L.; Abrahamsen,
(
Weiland, G. A.; Oswald, R. E. Dynamics of cleft closure of the GluA2
ligand-binding domain in the presence of full and partial agonists
revealed by hydrogen-deuterium exchange. J. Biol. Chem. 2013, 288,
B.; Nielsen, B.; Gajhede, M.; Kastrup, J. S.; Jensen, A. A.; Pickering, D.
S.; Frydenvang, K.; Gefflaut, T.; Bunch, L. Chemoenzymatic synthesis
of new 2,4-syn-functionalized (S)-glutamate analogues and structure−
activity relationship studies at ionotropic glutamate receptors and
excitatory amino acid transporters. J. Med. Chem. 2013, 56, 1614−
1628.
2
(
7658−27666.
15) Bjerrum, E. J.; Kristensen, A. S.; Pickering, D. S.; Greenwood, J.
R.; Nielsen, B.; Liljefors, T.; Schousboe, A.; Brauner-Osborne, H.;
̈
3
Madsen, U. Design, synthesis, and pharmacology of a highly
subtypeselective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hy-
droxy-5-isoxazolyl)propionic acid (Cl-HIBO). J. Med. Chem. 2003,
(31) Ransom, R. W.; Stec, N. L. Cooperative modulation of [ H]MK-
801 binding to the N-methyl-D-aspartate receptor ion channel
complex by L-glutamate, glycine, and polyamines. J. Neurochem.
1988, 51, 830−836.
4
(
6, 2246−2249.
16) Frydenvang, K.; Pickering, D. S.; Greenwood, J. R.; Krogsgaard-
(32) Sagot, E.; Pickering, D. S.; Pu, X.; Umberti, M.; Stensbol, T. B.;
Nielsen, B.; Chapelet, M.; Bolte, J.; Gefflaut, T.; Bunch, L. Chemo-
enzymatic synthesis of a series of 2,4-syn-functionalized (S)-glutamate
analogues: new insight into the structure-activity relation of ionotropic
glutamate receptor subtypes 5, 6, and 7. J. Med. Chem. 2008, 51,
4093−4103.
Larsen, N.; Brehm, L.; Nielsen, B.; Vogensen, S. B.; Hald, H.; Kastrup,
J. S.; Krogsgaard-Larsen, P.; Clausen, R. P. Biostructural and
pharmacological studies of bicyclic analogues of the 3-isoxazolol
glutamate receptor agonist ibotenic acid. J. Med. Chem. 2010, 53,
8
(
354−8361.
17) Vogensen, S. B.; Clausen, R. P.; Greenwood, J. R.; Johansen, T.
̈
(33) Strange, M.; Brauner-Osborne, H.; Jensen, A. A. Functional
N.; Pickering, D. S.; Nielsen, B.; Ebert, B.; Krogsgaard-Larsen, P.
Convergent synthesis and pharmacology of substituted tetrazolyl-2-
amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid analogues. J.
Med. Chem. 2005, 48, 3438−3442.
characterization of homomeric ionotropic glutamate receptors GluR1-
GluR6 in a fluorescence-based high throughput screening assay. Comb.
Chem. High Throughput Screening 2006, 9, 147−158.
̇
(34) Juknaite, L.; Sugamata, Y.; Tokiwa, K.; Ishikawa, Y.;
(
18) Vogensen, S. B.; Frydenvang, K.; Greenwood, J. R.; Postorino,
Takamizawa, S.; Eng, A.; Sakai, R.; Pickering, D. S.; Frydenvang, K.;
Swanson, G. T.; Kastrup, J. S.; Oikawa, M. Studies on an (S)-2-amino-
3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor
antagonist IKM-159: asymmetric synthesis, neuroactivity, and
structural characterization. J. Med. Chem. 2013, 56, 2283−2293.
(35) Krintel, C.; Frydenvang, K.; Ceravalls de Rabassa, A.; Kaern, A.
M.; Gajhede, M.; Pickering, D. S.; Kastrup, J. S. L-Asp is a useful tool
in the purification of the ionotropic glutamate receptor A2 ligand-
binding domain. FEBS J. 2014, 281, 2422−2430.
G.; Nielsen, B.; Pickering, D. S.; Ebert, B.; Bølcho, U.; Egebjerg, J.;
Gajhede, M.; Kastrup, J. S.; Johansen, T. N.; Clausen, R. P.;
Krogsgaard-Larsen, P. A tetrazolyl substituted subtype-selective
AMPA receptor agonist. J. Med. Chem. 2007, 50, 2408−2414.
(
19) Jensen, A. A.; Christesen, T.; Bølcho, U.; Greenwood, J. R.;
Postorino, G.; Vogensen, S. B.; Johansen, T. N.; Egebjerg, J.; Brauner-
Osborne, H.; Clausen, R. P. Functional characterization of Tet-AMPA
tetrazolyl-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic
̈
[
acid] analogues at ionotropic glutamate receptors GluR1-GluR4. The
molecular basis for the functional selectivity profile of 2-Bn-Tet-
AMPA. J. Med. Chem. 2007, 50, 4177−4185.
(36) Ursby, T.; Unge, J.; Appio, R.; Logan, D. T.; Fredslund, F.;
Svensson, C.; Larsson, K.; Labrador, A.; Thunnissen, M. M. The
macromolecular crystallography beamline I911−3 at the MAX IV
laboratory. J. Synchrotron Radiat. 2013, 20, 648−653.
(
20) Stawski, P.; Sumser, M.; Trauner, D. A photochromic agonist of
AMPA receptors. Angew. Chem., Int. Ed. 2012, 51, 5748−5751.
(37) Kabsch, W. Integration, scaling, space-group assignment and
post-refinement. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 66,
133−144.
(
21) Laprell, L.; Hull, K.; Stawski, P.; Schon, C.; Michalakis, S.; Biel,
̈
̈
M.; Sumser, M. P.; Trauner, D. Restoring light sensitivity in blind
retinae using a photochromic AMPA receptor agonist. ACS Chem.
Neurosci. 2016, 7, 15.
(38) Leslie, A. G. W.; Powell, H. R. Processing diffraction data with
mosflm. Evolving Methods for Macromolecular Crystallography; Spring-
er: Dordrecht, The Netherlands, 2007; Vol. 245, pp 41−51.
(39) Evans, P. R. An introduction to data reduction: space-group
determination, scaling and intensity statistics. Acta Crystallogr., Sect. D:
Biol. Crystallogr. 2011, 67, 282−292.
(40) Winn, M. D.; Ballard, C. C.; Cowtan, K. D.; Dodson, E. J.;
Emsley, P.; Evans, P. R.; Keegan, R. M.; Krissinel, E. B.; Leslie, A. G.;
McCoy, A.; McNicholas, S. J.; Murshudov, G. N.; Pannu, N. S.;
Potterton, E. A.; Powell, H. R.; Read, R. J.; Vagin, A.; Wilson, K. S.
Overview of the CCP4 suite and current developments. Acta
Crystallogr., Sect. D: Biol. Crystallogr. 2011, 67, 235−242.
(
22) Banke, T. G.; Greenwood, J. R.; Christensen, J. K.; Liljefors, T.;
Traynelis, S. F.; Schousboe, A.; Pickering, D. S. Identification of amino
acid residues in GluR1 responsible for ligand binding and
desensitization. J. Neurosci. 2001, 21, 3052−3062.
(
23) Lau, A. Y.; Roux, B. The hidden energetics of ligand binding and
activation in a glutamate receptor. Nat. Struct. Mol. Biol. 2011, 18,
83−287.
24) Armstrong, N.; Gouaux, E. Mechanisms for activation and
2
(
antagonism of an AMPA-sensitive glutamate receptor: crystal
structures of the GluR2 ligand binding core. Neuron 2000, 28, 165−
181.
(41) McCoy, A. J.; Grosse-Kunstleve, R. W.; Adams, P. D.; Winn, M.
D.; Storoni, L. C.; Read, R. J. Phaser crystallographic software. J. Appl.
Crystallogr. 2007, 40, 658−674.
(
25) Pøhlsgaard, J.; Frydenvang, K.; Madsen, U.; Kastrup, J. S.
Lessons from more than 80 structures of the GluA2 ligand-binding
J
J. Med. Chem. XXXX, XXX, XXX−XXX