摘要:
The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.
摘要:
The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.
摘要:
Inhibitors of AMPA-type glutamate ion channels are useful as biochemical probes for structure-function studies and as drug candidates for a number of neurological disorders and diseases. Disclosed herein is the identification of an RNA inhibitor or aptamer by an in vitro evolution approach and characterization of its mechanism of inhibition on the sites of interaction by equilibrium binding and on the receptor channel-opening rate by a laser-pulse photolysis technique. The aptamer of the invention is a noncompetitive inhibitor of AMPA-type glutamate ion channels, one that selectively inhibits the GluA2Qflip AMPA receptor subunit without any effect on other AMPA receptor subunits or on kainate or NMDA receptors. Furthermore, the aptamer preferentially inhibits the closed-channel state of GluA2Qflip with a KI=1.5 μM or by ˜15-fold over the open-channel state. The potency and selectivity of this aptamer rival those of small molecule inhibitors. Together, these properties make the aptamers of the present invention promising water-soluble, highly potent, GluA2 subunit-selective drugs.
摘要:
The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.
摘要:
The present invention relates to novel nucleic acid ligands or aptamers that demonstrate potent and selective inhibition of the open-channel conformation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors.
摘要:
The present invention relates to novel nucleic acid ligands or aptamers that demonstrate potent and selective inhibition of the open-channel conformation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors.
摘要:
The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.
摘要:
Inhibitors of AMPA-type glutamate ion channels are useful as biochemical probes for structure-function studies and as drug candidates for a number of neurological disorders and diseases. Disclosed herein is the identification of an RNA inhibitor or aptamer by an in vitro evolution approach and characterization of its mechanism of inhibition on the sites of interaction by equilibrium binding and on the receptor channel-opening rate by a laser-pulse photolysis technique. The aptamer of the invention is a noncompetitive inhibitor of AMPA-type glutamate ion channels, one that selectively inhibits the GluA2Qflip AMPA receptor subunit without any effect on other AMPA receptor subunits or on kainate or NMDA receptors. Furthermore, the aptamer preferentially inhibits the closed-channel state of GluA2Qflip with a KI=1.5 μM or by ˜15-fold over the open-channel state. The potency and selectivity of this aptamer rival those of small molecule inhibitors. Together, these properties make the aptamers of the present invention promising water-soluble, highly potent, GluA2 subunit-selective drugs.
摘要:
The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.