Solid-phase synthesis of Stat3 inhibitors incorporating O-carbamoylserine and O-carbamoylthreonine as glutamine mimics
Solid-phase synthesis of Stat3 inhibitors incorporating O-carbamoylserine and O-carbamoylthreonine as glutamine mimics
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DOI：
10.1016/j.bmcl.2006.10.099
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发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
McMurray, John S.
中科院分区：
文献类型：
--
作者：
Mandal, Pijus K.;Heard, Patricia A.;McMurray, John S.
O-氨甲酰基苏氨酸和O-氨甲酰基苏氨酸是谷氨酰胺类似物，其被掺入Stat 3抑制肽中以探测pY+3位置处的Gln的需求。将Fmoc-Ser-NHBn和Fmoc-Thr-NHBn转化为碳酸硝基苯酯，并通过侧链氨基甲酸酯键连接到Rink树脂上。肽组装后，酸处理产生含O-氨基甲酰基丝氨酸和O-氨基甲酰基苏氨酸的肽。对Stat 3的亲和力顺序为Gln> Ser（CONH 2）> Thr（CONH 2），表明谷氨酰胺侧链的相对紧密的结合口袋。(c)2006爱思唯尔有限公司保留所有权利。
O-Carbamoyiserine and O-carbamoylthreonine are glutamine analogues that were incorporated into a Stat3 inhibitory peptide to probe the requirements of Gin at the pY+3 position. Fmoc-Ser-NHBn and Fmoc-Thr-NHBn were converted to nitrophenyl carbonates and were attached to Rink resin via a side-chain carbamate linkage. After assembly of the peptide, acid treatment resulted in O-carbamoylserine and O-carbamoylthreonine-containing peptides. The order of affinity for Stat3 was Gin > Ser (CONH2) > Thr(CONH2) suggesting a relatively tight binding pocket for the side chain of glutamine. (c) 2006 Elsevier Ltd. All rights reserved.