An easily accessible, lower rim substituted calix[4]arene selectively binds N,N-dimethyllysine

Abstract

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.