کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1932043 | 1050572 | 2010 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin](/preview/png/1932043.png)
The category A agent, botulinum neurotoxin (BoNT), is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, we have identified three RNA aptamers through SELEX-process, which bind strongly to the light chain of type A BoNT (BoNT/A) and inhibit the endopeptidase activity, with IC50 in low nM range. Inhibition kinetic studies reveal low nM KI and non-competitive nature of their inhibition. Aptamers are unique group of molecules as therapeutics, and this is first report of their development as an antidote against botulism. These data on KI and IC50 strongly suggest that the aptamers have strong potential as antidotes that can reverse the symptom caused by BoNT/A.
Journal: Biochemical and Biophysical Research Communications - Volume 396, Issue 4, 11 June 2010, Pages 854–860