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

Area of Science:

• Biochemistry
• Chemical Biology
• Molecular Recognition

Background:

• Post-translational modifications (PTMs) regulate protein function.
• N-methylated lysine (Kme) and arginine (Rme) are key PTMs.
• Selective binding of lower lysine methylation states (e.g., Kme2) is difficult.

Purpose of the Study:

• To develop a host molecule for selective N,N-dimethyllysine (Kme2) binding.
• To investigate the binding properties and conformational dynamics of the novel host.

Main Methods:

• Synthesis of a modified p-sulfonatocalix[4]arene host.
• Solution-based binding assays.
• Characterization of host-guest interactions and molecular dynamics.

Main Results:

• A single-step synthesis yielded a potent Kme2-selective host.
• The host demonstrates efficient and selective binding of Kme2.
• Unusual conformational dynamics correlate with guest-binding properties.

Conclusions:

• The novel sulfonate ester-modified calixarene is an effective Kme2-selective host.
• This provides a new tool for studying Kme2-regulated biological processes.
• Understanding the host's dynamics offers insights into molecular recognition mechanisms.