Ginkgolides and glycine receptors: a structure-activity relationship study
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Ginkgolides and glycine receptors : a structure-activity relationship study. / Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.; Strømgaard, Kristian.
In: Chemistry: A European Journal, Vol. 10, No. 6, 2004, p. 1507-18.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Ginkgolides and glycine receptors
T2 - a structure-activity relationship study
AU - Jaracz, Stanislav
AU - Nakanishi, Koji
AU - Jensen, Anders A.
AU - Strømgaard, Kristian
PY - 2004
Y1 - 2004
N2 - Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown that native ginkgolides are potent and selective antagonists of the inhibitory glycine receptor. Forty new ginkgolide derivatives have been prepared in good to high yields on milligram scales and investigated for their antagonistic properties at homomeric alpha 1 glycine receptors, thus providing the first structure-activity relationship study of ginkgolides at glycine receptors. A high-throughput screening assay showed that native ginkgolide C was the most potent ligand, and that manipulation of any of the hydroxyl groups led to loss of activity at alpha 1 glycine receptors.
AB - Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown that native ginkgolides are potent and selective antagonists of the inhibitory glycine receptor. Forty new ginkgolide derivatives have been prepared in good to high yields on milligram scales and investigated for their antagonistic properties at homomeric alpha 1 glycine receptors, thus providing the first structure-activity relationship study of ginkgolides at glycine receptors. A high-throughput screening assay showed that native ginkgolide C was the most potent ligand, and that manipulation of any of the hydroxyl groups led to loss of activity at alpha 1 glycine receptors.
KW - Diterpenes
KW - Ginkgolides
KW - Heterocyclic Compounds with 4 or More Rings
KW - Lactones
KW - Ligands
KW - Molecular Conformation
KW - Receptors, Glycine
KW - Structure-Activity Relationship
U2 - 10.1002/chem.200305473
DO - 10.1002/chem.200305473
M3 - Journal article
C2 - 15034895
VL - 10
SP - 1507
EP - 1518
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
SN - 0947-6539
IS - 6
ER -
ID: 38485015