@article{lins_miloslavina_avrutina_theiss_hofmann_kolmar_buntkowsky_2024, title={Enhancing Sensitivity of Nuclear Magnetic Resonance in Biomolecules: Parahydrogen-Induced Hyperpolarization in Synthetic Disulfide-Rich Miniproteins}, ISSN={["1520-5126"]}, DOI={10.1021/jacs.4c11589}, abstractNote={Hyperpolarization of small peptides by parahydrogen-induced polarization (PHIP) to increase the sensitivity of nuclear magnetic resonance (NMR) techniques is well established, while its application to larger biopolymers is still a mainly unexplored area. A particular challenge is the presence of folding-essential disulfide bridges. They tend to form metal complexes, thus hampering catalytic hydrogenation, a prerequisite for PHIP. We applied the PHIP technique to enhance NMR signal intensity in cystine-knot miniproteins─highly ordered peptide architectures covalently stabilized by three disulfides. To achieve PHIP, we introduced an l-propargyl tyrosine label at different positions in three synthetic open-chain variants of a natural trypsin inhibitor MCoTI-II. For the folded cystine knot, we observed NMR signal enhancements of up to 499 in methanol, 307 in a D}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Lins, Jonas and Miloslavina, Yuliya A. and Avrutina, Olga and Theiss, Franziska and Hofmann, Sarah and Kolmar, Harald and Buntkowsky, Gerd}, year={2024}, month={Dec} }