Amino Acid‐Derived Sensors for Specific Zn²⁺ Detection Using Hyperpolarized ¹³C Magnetic Resonance Spectroscopy

Abstract

Alterations in Zn2+ concentration are seen in normal tissues and in disease states, and for this reason imaging of Zn2+ is an area of active investigation. Herein, enriched [1‐13C]cysteine and [1‐13C2]iminodiacetic acid were developed as Zn2+‐specific imaging probes using hyperpolarized 13C magnetic resonance spectroscopy. [1‐13C]cysteine was used to accurately quantify Zn2+ in complex biological mixtures. These sensors can be employed to detect Zn2+ via imaging mechanisms including changes in 13C chemical shift, resonance linewidth, or T1.

Entwicklung molekularer Sonden für die hyperpolarisierte NMR‐Bildgebung im biologischen Bereich

“…Zum spezifischen Zn 2+ -Nachweis wurden [1-13 C]-Cystein und [1- 13 C 2 ]-Iminodiessigsäure als molekulare Sonden entwickelt. [63] 15 N-o-Aminophenol-N,N,O-triessigsäure ( 15 N-APTRA; Abbildung 6C)i st ein langlebiger hyperpolarisierter Ca 2+ -Chelator. [60] Das kleine gyromagnetische Verhältnis des 15 N-Kerns trägt zum relativ großen T 1 -Wert bei (37 so hne Ca 2+ und 36 sm it Ca 2+ bei 9.4 T).…”

“…Es wurde auch demonstriert, dass hyperpolarisierte 13 C‐markierte EGTA μ m Konzentrationen an Ca 2+ in vitro nachweisen kann. Zum spezifischen Zn 2+ ‐Nachweis wurden [1‐ 13 C]‐Cystein und [1‐ 13 C 2 ]‐Iminodiessigsäure als molekulare Sonden entwickelt [63] …”

Mobile zinc as a modulator of sensory perception

“…In cells and live tissue slices, TPA removes zinc from fluorescence sensors more than twice as fast as TPEN [ 93 ]. The lower cellular toxicity associated with TPA makes it attractive for studies in a wide variety of biological contexts [ 48 , 94 , 95 , 96 , 97 , 98 ]. Although there is some evidence that TPA chelates metal ions other than zinc(II), particularly copper(I), it does not appear to substantially affect the concentrations of these ions at the less toxic and membrane‐permeable levels where it has typically been applied [ 99 , 100 ].…”

Design of Nuclear Magnetic Resonance Molecular Probes for Hyperpolarized Bioimaging

“…It was also confirmed that hyperpolarized 13 C‐labeled EGTA can detect μ m levels of Ca 2+ in vitro. As for Zn 2+ , [1‐ 13 C] cysteine and [1‐ 13 C 2 ] iminodiacetic acid were developed as molecular probes for specific Zn 2+ detection [63] …”