Synthesis of N-Boc protected hydrazine diacids as key structural units for the formation of alpha-helix mimics.
Synthesis of N-Boc protected hydrazine diacids as key structural units for the formation of alpha-helix mimics.
复制标题
N-Boc 保护的肼二酸的合成作为形成 α-螺旋模拟物的关键结构单元。
DOI：
10.1007/978-0-387-73657-0_97
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发表时间：
2009
影响因子：
--
通讯作者：
McLaughlin,MarkL
中科院分区：
文献类型：
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作者：
Anderson,Laura;Topper,Melissa;Jain,Priyesh;McIntosh,Emily;McLaughlin,MarkL
许多疾病，如自身免疫、癌症、炎症和神经退行性疾病都是凋亡过程失调的结果。在B细胞淋巴瘤-2（Bcl-2）家族中，抗凋亡蛋白和促凋亡蛋白的整体相互作用在调节细胞凋亡方面发挥着重要作用。一些研究已经证明，抗凋亡Bcl-2和Bcl-xL蛋白的过表达与肿瘤进展和耐药性相关[1]。先前报道的抑制促凋亡BH 3结构域和Bcl-2家族蛋白之间相互作用的肽模拟物含有疏水性支架，这将减少其作为潜在药物的用途[2]。我们报告了用于形成基于肼连接的哌嗪-2，6-二酮支架的更亲水化合物的关键单体构建块的合成（图1）。
Many diseases, such as autoimmunity, cancer, inflammatory, and neurodegenerative disorders are the result of disregulation of the apoptotic process. Within the B-cell lymphoma-2 (Bcl-2) family, the overall interaction of anti and pro-apoptotic proteins play a major role in regulating apoptosis. Several studies have demonstrated that overexpression of anti-apoptotic Bcl-2 and Bcl-xL proteins is associated with tumor progression and drug resistance [1]. Previously reported peptidomimetics that inhibit the interaction between pro-apoptotic BH3 domains and Bcl-2 family proteins contain hydrophobic scaffolds that would diminish their use as potential drugs [2]. We report the synthesis of key monomer building blocks for the formation of more hydrophilic compounds based on hydrazine linked piperazine-2, 6-dione scaffolds (Figure 1).