PuSH - Publication Server of Helmholtz Zentrum München

Chang, T.W.* ; Blank, M. ; Janardhanan, P.* ; Singh, B.R.* ; Mello, C.* ; Blind, M.* ; Cai, S.W.*

In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin.

Biochem. Biophys. Res. Commun. 396, 854-860 (2010)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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 K-1 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 K-1 and IC50 strongly suggest that the aptamers have strong potential as antidotes that can reverse the symptom caused by BoNT/A.
Altmetric
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords RNA; Aptamer; Botulinum neurotoxin; Antidote; Endopeptidase
ISSN (print) / ISBN 0006-291X
e-ISSN 1090-2104
Quellenangaben Volume: 396, Issue: 4, Pages: 854-860 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place San Diego
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Hematopoetic Cell Transplants (IMI-KHZ)