Programming A Molecular Relay for Ultrasensitive Biodetection through (129)Xe NMR

Area of Science:

• Supramolecular chemistry
• Chemical biology
• Nuclear Magnetic Resonance (NMR) spectroscopy

Background:

• Protein detection in complex biological media remains challenging.
• Hyperpolarized (129)Xe NMR offers high sensitivity but requires specific molecular tools.
• Supramolecular cages like cucurbiturils can be engineered for molecular recognition.

Purpose of the Study:

• To develop a supramolecular strategy for specific protein detection in complex environments.
• To utilize a molecular relay system with hyperpolarized (129)Xe NMR for ultrasensitive detection.
• To demonstrate the adaptability of the system for different protein targets.

Main Methods:

• Design and synthesis of a two-faced guest (TFG) molecule.
• Programming a cucurbit[6]uril (CB[6])-based molecular relay.
• Utilizing X-ray crystallography to confirm molecular interactions.
• Employing ultrasensitive (129)Xe NMR spectroscopy for signal detection.

Main Results:

• A molecular relay was successfully designed to bind cucurbit[6]uril and block xenon interaction until protein recruitment.
• The system demonstrated specific detection of carbonic anhydrase II (CAII) in buffer and E. coli cultures.
• The molecular relay was reprogrammed to detect avidin, showcasing its versatility.
• X-ray crystallography confirmed the mechanism of protein-mediated TFG displacement.

Conclusions:

• The developed supramolecular strategy enables sensitive and specific protein detection via (129)Xe NMR.
• The molecular relay system is adaptable for detecting various protein analytes.
• This approach holds promise for protein analysis in complex biological systems.