Advances in Parahydrogen‐Induced Polarization for Nuclear Magnetic Resonance of Peptides, Proteins, and Biopolymers

Hyperpolarization techniques like parahydrogen‐induced polarization significantly enhance nuclear magnetic resonance (NMR) sensitivity but have been underexplored for larger biomolecules and biopolymers. Here, after a short introduction into parahydrogen‐based hyperpolarization, a number of recent examples of efficient PHIP labeling of amino acids, peptides, mini‐proteins, and biopolymers using nonnatural amino acids with unsaturated side chains from the Darmstadt group are presented. Employing solid‐phase peptide synthesis and postsynthetic modifications, it is possible to achieve strong hyperpolarization enhancements of typically three orders of magnitude in peptides such as SFTI‐1, octreotide, and the miniprotein MCoTI‐II, while preserving their bioactivity. Even in the 236 kDa synthetic biopolymer poly‐ γ ‐(4‐propargyloxy)‐benzyl‐L‐glutamate) enhancements of 800 and more are obtained. These advancements facilitate rapid, sensitive NMR detection of complex biomolecules and open new experimental possibilities in biochemical research, medical diagnostics, and related fields.