Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Institute of Physical Chemistry, Technical University Darmstadt, Alarich-Weiss-Straße 8, 64287, Darmstadt, Germany.
Chembiochem. 2021 Mar 2;22(5):855-860. doi: 10.1002/cbic.202000711. Epub 2020 Nov 19.
The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide.
生物相关的 PyFALGEA 寡肽配体对表皮生长因子受体（EGFR）具有选择性，已成功用作磁共振信号放大的可逆交换（SABRE）实验中的底物。证明 PyFALGEA 和铱催化剂 IMes 形成 PyFALGEA:IMes 分子络合物。PyFALGEA:IMes 和 H 之间的相互作用导致形成三元 SABRE 络合物。选择性 1D EXSY 实验表明该络合物不稳定，这是 SABRE 成功实现超极化的必要条件。观察到从 para-氢气到 PyFALGEA 的极化转移，导致 PyFALGEA 的 H NMR 信号显著增强。检查了不同的铱催化剂和肽，以讨论它们的分子结构对超极化效率的影响。观察到，当使用具有空间要求较低的 NHC 配体系统（如 IMesBn）的铱催化剂时，PyFALGEA 寡肽的超极化效率更高。使用 PyFALGEA 的较短类似物 PyLGEA 和 PyEA 的实验表明，来自 PyFALGEA 寡肽的大体积苯丙氨酸在 SABRE 络合物中引起空间位阻，这阻碍了与 IMes 的超极化。最后，用 IMesBn 进行的 PyFALGEA 的单个扫描 H NMR SABRE 实验在氢化物区域显示出独特的 NMR 线图案，可视为这种重要寡肽的指纹。
