Crosslinked Aspartic Acids as Helix-Nucleating Templates

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• 作者：Dr. Hui Zhao ; Dr. Qi-Song Liu ; Dr. Hao Geng ; Dr. Yuan Tian ; Dr. Min Cheng ; Dr. Yan-Hong Jiang ; Dr. Ming-Sheng Xie ; Dr. Xiao-Gang Niu ; Dr. Fan Jiang ; Prof. Dr. Ya-Ou Zhang ; Dr. Yuan-Zhi Lao ; Prof. Dr. Yun-Dong Wu ; Prof. Dr. Nai-Han Xu and Prof. Dr. Zi-Gang Li
• 刊名：Angewandte Chemie
• 出版年：2016
• 出版时间：September 19, 2016
• 年：2016
• 卷：128
• 期：39
• 页码：12267-12272
• 全文大小：2631K
• ISSN：1521-3757

文摘

Described is a facile helix-nucleating template based on a tethered aspartic acid at the N-terminus [terminal aspartic acid (TD)]. The nucleating effect of the template is subtly influenced by the substituent at the end of the side-chain-end tether as indicated by circular dichroism, nuclear magnetic resonance, and molecular dynamics simulations. Unlike most nucleating strategies, the N-terminal amine is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators (PERMs) constructed using this strategy show improved therapeutic properties. The current strategy can be regarded as a good complement to existing helix-stabilizing methods.