A Strategy to Design Hyperpolarized 13 C Magnetic Resonance Probes Using [1-13 C]α-Amino Acid as a Scaffold Structure

Abstract

Hyperpolarization is an emerging method that dramatically enhances NMR signal intensity. As a result of their increased sensitivity, hyperpolarized (HP) NMR molecular probes can be used to perform time-resolved spectroscopy and imaging in vitro and in vivo. It is, however, challenging to design such probes de novo. Herein, the [1-¹³ C]α-amino acid is reported as a scaffold structure to design HP ¹³ C NMR molecular probes. The [1-¹³ C]α-amino acid can be converted to various HP ¹³ C chemical probes that show sufficient chemical shift change by altering the chemical state of the α nitrogen upon interaction with the target. Several previously reported HP probes could be explained by this design principle. To demonstrate the versatility of this approach, two α-amino-acid-based HP ¹³ C chemical probes, sensitive to pH and Ca²⁺ ion, were developed and used to detect targets.

Keywords: NMR spectroscopy; amino acids; biosensors; dynamic nuclear polarization; hyperpolarization.