Parahydrogen‐Induced Polarization of a Labeled, Cancer‐Targeting DNA Aptamer

Abstract

Enhancing NMR signals of biomacromolecules by hyperpolarization offers exciting opportunities for diagnostic applications. However, their hyperpolarization via parahydrogen remains challenging as specific catalytic interactions are required, which are difficult to tune due to the large size of the biomolecule and its insolubility in organic solvents. Herein, we show the unprecedented hyperpolarization of the cancer-targeting DNA aptamer AS1411. By screening different molecular motifs for an unsaturated label in nucleosides and in DNA oligomers, we were able to identify structural prerequisites for the hyperpolarization of AS1411. Finally, adjusting the polarity of AS1411 by complexing the DNA backbone with amino polyethylene glycol chains allowed the hydrogenation of the label with parahydrogen while the DNA structure remains stable to maintain its biological function. Our results are expected to advance hyperpolarized molecular imaging technology for disease detection in the future.

A Straightforward Method for the Generation of Hyperpolarized Orthohydrogen with a Partially Negative Line

“…Finally, the hyperpolarized ligand is released. The vast majority of PHIP research concentrates on the efficient hyperpolarization of molecules and their applications; notably, the hyperpolarization of molecular systems, which can be employed in medical diagnostics or catalysis [25–31] . Although one might suppose that all about o‐H 2 NMR is already known, it has recently been observed that hyperpolarized o‐H 2 can be produced from p‐H 2 during the hPHIP process.…”

“…The vast majority of PHIP research concentrates on the efficient hyperpolarization of molecules and their applications; notably, the hyperpolarization of molecular systems, which can be employed in medical diagnostics or catalysis. [25][26][27][28][29][30][31] Although one might suppose that all about o-H 2 NMR is already known, it has recently been observed that hyperpolarized o-H 2 can be produced from p-H 2 during the hPHIP process. Additionally, what is more interesting is that the hyperpolarized o-H 2 manifests as an antiphase signal, and is known as the Partially Negative Line (PNL) effect.…”

Synthesis and properties of 6-alkynyl-5-aryluracils

“…The first alkyne-linked compound was already published in 1976, accompanied by new synthesis methods in the following years [24][25][26][27]. With the discovery of potential antiviral properties and other synthetic opportunities, alkyne-linked derivatives remained an integral part of research to the present day [28][29][30][31][32][33][34][35]. However, the main methods known so far are to substitute uracil either only at position 6 or at position 5 [26][27][28][34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”