%0 Journal Article
%T Construction of superagonist mutein of human CNTF and its expression in Pichia pastoris<br>高比活人睫状神经营养因子突变体基因的构建及其在巴斯德毕赤酵母中的表达
%A ZHAO Hong-liang
%A XUE Chong
%A XIONG Xiang-Hua
%A ZHANG Wei
%A LIU Zhi-min
%A <br>赵洪亮
%A 薛冲
%A 熊向华
%A 张伟
%A 刘志敏
%J 微生物学报
%D 2005
%I 
%X Human ciliary neurotrophic factor (hCNTF) and its derivatives are promising therapeutics for obesity associated with diabetes. To reduce its side effects and increase its efficacy, superagonist mutein of human CNTF was constructed by the introduction of S165D/Q166H mutation into AX15(R13K), which is a mutein of naturally occurring hCNTF, with improved biological activity, stability, solubility and KEX2 resistance.In vitro TF_1 cell survival assay andin vivo antiobesity tests showed DH_AX(R13K) was about 5 fold more potent than AX15(R13K). It was further demonstrated that the antiobesity effect of DH_AX15(R13K) was more durable than that of AX15(R13K). The more durable effects of DH_AX15(R13K) is ascribed to its higher specific activity, but not to its prolonged half-life. The superagonist mutein of human CNTF would have an improved side effect profile and thus have superior therapeutic potential.
%K Superagonist mutein
%K Ciliary neurophic factor
%K Pichia pastoris<br>睫状神经营养因子
%K 高比活突变体
%K 巴斯德毕赤酵母
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=A3C6BA55AB623B90FA9104CFFC826F3C&aid=569C56C94E8C3A3B&yid=2DD7160C83D0ACED&vid=94E7F66E6C42FA23&iid=38B194292C032A66&sid=5A735990D5DE8BF4&eid=7D6CD8918B045FD4&journal_id=0001-6209&journal_name=微生物学报&referenced_num=0&reference_num=10