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Developing glutamate receptor Aptamers as drug candidates

Developing glutamate receptor Aptamers as drug candidates

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Li Niu Department of Chemistry,and the Center for Neuroscience Research,State University of New York(SUNY)at Albany, Albany,New York,12222,USA

＜正＞In finding a new treatment for a number of neurological disorders and diseases,such as epilepsy,stroke and amyotrophic lateral sclerosis（ALS）,one of the potential therapeutic strategies is to develop inhibitors for theα-amino- 3-hydroxy-5-methyl-4-isoxazole propionic acid（AMPA） receptors,a receptor subtype in the glutamate ion channel receptor *** is because excessive activity of AMPA receptors leads to abnormal calcium influx into neurons, which in turn leads to cell *** developing AMPA receptor inhibitors that are both potent and water soluble,we have used systematic evolution of ligands by exponential enrichment（SELEX） and have successfully identified three classes of aptamers with nanomolar affinity against AMPA *** the class of competitive aptamers,we found one aptamer with an IC50 value of 30 nM,rivaling any other exiting AMPA receptor ***,this aptamer is broadly active in all AMPA receptor subunits,but has no unwanted activity in either kainate or NMDA receptors,the two other glutamate receptor *** have also identified two other classes of noncompetitive aptamers that are selective to different conformations of GluR2,a key AMPA receptor subunit that mediates glutamateinduced cell *** class uniquely inhibits the open-channel conformation whereas the other inhibits the closedchannel conformation of *** latter in fact is single-subunit selective aptamer designed to target GluR2 *** turn these aptamers into potentially useful drugs,we have now successfully developed a class of chemically modified aptamers that are highly resistant to ribonucleases so that these aptamers can be tested in *** results demonstrate the possibility of developing RNA aptamers against AMPA receptor channels with nanomolar affinity,excellent water solubility and superior selectivity to AMPA receptors and even to a single AMPA receptor *** aptamers are therefore potential templates for design of better in

关键词： glutamate ion channels RNA aptamers SELEX

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