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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
In vitro selection of RNA aptamers that inhibit the activity of type A botulinum neurotoxin.
Biochem. Biophys. Res. Commun. 396, 854-860 (2010)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
RNA; Aptamer; Botulinum neurotoxin; Antidote; Endopeptidase
ISSN (print) / ISBN
0006-291X
e-ISSN
1090-2104
Quellenangaben
Band: 396,
Heft: 4,
Seiten: 854-860
Verlag
Elsevier
Verlagsort
San Diego
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Hematopoetic Cell Transplants (IMI-KHZ)