Parahydrogen‐Induced Polarization of Amino Acids

Abstract

Nuclear magnetic resonance (NMR) has become a universal method for biochemical and biomedical studies, including metabolomics, proteomics, and magnetic resonance imaging (MRI). By increasing the signal of selected molecules, the hyperpolarization of nuclear spin has expanded the reach of NMR and MRI even further (e.g. hyperpolarized solid‐state NMR and metabolic imaging in vivo). Parahydrogen (pH2) offers a fast and cost‐efficient way to achieve hyperpolarization, and the last decade has seen extensive advances, including the synthesis of new tracers, catalysts, and transfer methods. The portfolio of hyperpolarized molecules now includes amino acids, which are of great interest for many applications. Here, we provide an overview of the current literature and developments in the hyperpolarization of amino acids and peptides.

Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives

“…Furthermore, the complexity of published hyperpolarized urine spectra [6][7][8][9] demonstrates that even the catalyst's limited chemical scope allows for the detection of large numbers of metabolites. The list of known 2 binding analytes is growing and includes, on top of nitrogenous heteroaromatics, pyruvate [10], tagged oligopeptides [11,12], amino acids [13,14], nitriles [15], and sulfur heteroaromatics [16], suggesting the chemoselectivity envelope is wide.…”

A disintegrin derivative as a case study for PHIP labeling of disulfide bridged biomolecules

“…That’s why the target system must be known precisely in advance 17 , 18 . Besides this enzymatic approach, non-canonical amino acids that contain different functional groups (ethynyl- 19 , azido- 20 , halogen- 21 ), can be incorporated into the peptide’s sequence and further utilized 12 , 15 , 22 – 33 . However, this process is exceptionally labor-intensive and proceeds with only low yields 34 .…”

Hyperpolarization of 15N in an amino acid derivative

“…[28][29][30][31][32][33] Another way to make use of para-hydrogen is to hydrogenate an unsaturated bond in a substrate and subsequently transfer the magnetization to a heteronucleus in the same molecule. [34][35][36][37] Especially in the case of small molecules, attaching an unsaturated sidearm to the compound one desires to polarize can be a facile way to access polarized compounds. Aer reacting the modied compound with para-hydrogen, the magnetization is transferred to a heteronucleus in the compound and the sidearm can be cleaved off by, e.g.…”

“…48,49 To that extend, several techniques have been applied. 37,50 Despite having hyperpolarized amino acids or their derivatives with PHIP by SABRE, 51,52 PHIP [53][54][55] and PHIP-SAH, 50,56 so far no attempts have been conducted to hyperpolarize the 15 N of the amino function of perdeuterated, 15 N-labelled amino acid derivatives with long T 1 .…”