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Crosslinked Aspartic Acids as Helix‐Nucleating Templates |
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| Authors: | 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 Prof. Dr. Zi‐Gang Li |
| Affiliation: | 1. School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, China;2. Shenzhen Key Lab of Tissue Engineering, The Second People's Hospital of Shenzhen, Shenzhen, China;3. Key Lab in Healthy Science and Technology, Division of Life Science, Shenzhen Graduate School of Tsinghua University, Shenzhen, China;4. College of Chemistry and Molecular Engineering, Beijing Nuclear Magnetic Resonance Center, Peking University, Beijing, China;5. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China |
| Abstract: | 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. |
| Keywords: | amino acids circular dichroism helical structures peptides protein– protein interactions |