Department of Chemistry and Centre for Advanced Materials and Related Technologies (CAMTEC), University of Victoria, 3800 Finnerty Rd, Victoria, BC V8P 5C2, Canada.
Org Biomol Chem. 2021 Jun 2;19(21):4691-4696. doi: 10.1039/d1ob00524c.
Post-translational modifications (PTMs) are critical controllers of protein functions. One set of important PTMs are N-methylated side chains of lysine and arginine, which exist in several functionally distinct forms. Multiple groups have demonstrated the selective binding of the most hydrophobic family member, trimethyllysine (Kme3), using various macrocyclic hosts, but the selective binding of lower methylation states remains challenging. Herein we report that the installation of a sulfonate ester on the lower rim phenol of p-sulfonatocalix[4]arene efficiently generates a potent, N,N-dimethyllysine (Kme2)-selective host in one step from commercially available starting materials. We characterize its binding behaviors in solution, and examine the relationship between its unusual conformational dynamics and its guest-binding properties.
翻译后修饰（PTMs）是蛋白质功能的关键调控因子。一组重要的PTMs是赖氨酸和精氨酸的N-甲基化侧链，它们以几种功能不同的形式存在。多个研究小组已经证明了最疏水的家族成员三甲基赖氨酸（Kme3）能与各种大环主体发生选择性结合，但较低甲基化状态的选择性结合仍然具有挑战性。在此，我们报告，从市售起始原料出发，在对磺基杯[4]芳烃的下缘酚上安装磺酸酯，可一步高效生成一种强效的、对N，N-二甲基赖氨酸（Kme2）具有选择性的主体。我们表征了其在溶液中的结合行为，并研究了其不寻常的构象动力学与其客体结合性质之间的关系。
