Synthesis and biological evaluation of botulinum neurotoxin a protease inhibitors.
Synthesis and biological evaluation of botulinum neurotoxin a protease inhibitors.
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DOI：
10.1021/jm901852f
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发表时间：
2010-03-11
影响因子：
7.3
通讯作者：
Bowlin, Terry L.
中科院分区：
文献类型：
--
作者：
Li, Bing;Pai, Ramdas;Cardinale, Steven C.;Butler, Michelle M.;Peet, Norton P.;Moir, Donald T.;Bavari, Sina;Bowlin, Terry L.
NSC 240898先前通过筛选国家癌症研究所开放库多样性集被鉴定为肉毒杆菌神经毒素A轻链（BoNT/A LC）内肽酶抑制剂。已经合成了两种类型的类似物，并在基于FRET的酶测定中显示出抑制BoNT/A LC，并在基于HPLC的测定中得到证实。还评价了这两个系列的化合物对炭疽致死因子（LF）（一种不相关的金属蛋白酶）的抑制，以检查BoNT/A LC抑制的酶特异性。在这两个系列中针对BoNT/A LC的最有效的抑制剂是化合物12（IC 50 = 2.5 μM，FRET测定），其比先导结构有效4.4倍，并且对BoNT/A LC的选择性比炭疽LF金属蛋白酶高11.2倍。结构-活性关系研究揭示了对效力和酶特异性重要的结构特征。
NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogs have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of compounds have also been evaluated for inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor against BoNT/A LC in these two series is compound 12 (IC50 = 2.5 µM, FRET assay), which is 4.4-fold more potent than the lead structure, and 11.2-fold more selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure-activity relationship studies have revealed structural features important to potency and enzyme specificity.
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影响因子：
2.7
作者：
Burnett, J. C.;Wang, C.;Bavari, S.
通讯作者：
Bavari, S.
影响因子：
3.5
作者：
Schmidt, JJ;Stafford, RG
通讯作者：
Stafford, RG
影响因子：
4.8
作者：
Kumaran, Desigan;Rawat, Richa;Swaminathan, Subramanyam
通讯作者：
Swaminathan, Subramanyam
DOI：
10.1038/nrd1694
发表时间：
2005-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Burnett JC;Henchal EA;Schmaljohn AL;Bavari S
通讯作者：
Bavari S
影响因子：
3.5
作者：
Moe, Scott T.;Thompson, Andrew B.;Jacobson, Alan R.
通讯作者：
Jacobson, Alan R.