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

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. We present the unprecedented hyperpolarization of the cancer‐targeting aptamer AS1411 via parahydrogen. For that, we screened for suitable parahydrogen‐induced polarization (PHIP) labels, performed solid phase synthesis to incorporate the label into AS1411 and adapted the polarity of DNA via PEGylation to enable efficient, selective hydrogenation in organic solvents without affecting canonical nucleotides.