Post-Intoxication Inhibition of Botulinum Neurotoxin Serotype A within Neurons by Small-Molecule, Non-Peptidic Inhibitors 英文参考文献.docVIP

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Post-Intoxication Inhibition of Botulinum Neurotoxin Serotype A within Neurons by Small-Molecule, Non-Peptidic Inhibitors 英文参考文献.doc

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Post-Intoxication Inhibition of Botulinum Neurotoxin Serotype A within Neurons by Small-Molecule, Non-Peptidic Inhibitors 英文参考文献

Toxins 2011, 3, 207-217; doi:10.3390/toxins3030207 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Article Post-Intoxication Inhibition of Botulinum Neurotoxin Serotype A within Neurons by Small-Molecule, Non-Peptidic Inhibitors Gordon Ruthel 1,*, James C. Burnett 2, Jonathan E. Nuss 1, Laura M. Wanner 1, Lyal E. Tressler 1, Edna Torres-Melendez 1, Sarah J. Sandwick 1, Cary J. Retterer 1 and Sina Bavari 1,* 1 U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702; USA; E-Mails: jonathan.nuss@ (J.E.N.); laura.wanner@ (L.M.W.); lyal.tressler@ (L.E.T.); edna.torres-melendez@ (E.T.-M.); sarah.sandwick@uni-wuerzburg.de (S.J.S.); cary.retterer@ (C.J.R.) 2 SAIC-Frederick, Inc., National Cancer Institute at Frederick, Target Structure-Based Drug Discovery Group, P.O. Box B, Frederick, MD 21702, USA; E-Mail: burnettjames@ * Authors to whom correspondence should be addressed; E-Mails: gordon.ruthel@ (G.R.); sina.bavari@ (S.B.); Tel.: +1-301-619-8564 (G.R.); +1-301-619-4246 (S.B.); Fax: +1-301-619-1138. Received: 8 February 2011; in revised from: 10 March 2011 / Accepted: 11 March 2011 / Published: 15 March 2011 Abstract: Botulinum neurotoxins (BoNTs) comprise seven distinct serotypes that inhibit the release of neurotransmitter across neuromuscular junctions, resulting in potentially fatal flaccid paralysis. BoNT serotype A (BoNT/A), which targets synaptosomal-associated protein of 25kDa (SNAP-25), is particularly long-lived within neurons and requires a longer time for recovery of neuromuscular function. There are currently no treatments available to counteract BoNT/A after it has entered the neuronal cytosol. In this study, we examined the ability of small molecule non-peptidic inhibitors (SMNPIs) to prevent SNAP-25 cleavage post-intoxication of neurons. The progressive cleavage of SNAP-25 observed over 5 h following 1 h BoNT/A intoxication was prevented by