Magnetic Resonance Signal Amplification by Reversible Exchange of Selective PyFALGEA Oligopeptide Ligands Towards Epidermal Growth Factor Receptors

• Published in: Chembiochem : a European journal of chemical biology Vol. 22; no. 5; pp. 855 - 860
• Main Authors: Ratajczyk, Tomasz, Buntkowsky, Gerd, Gutmann, Torsten, Fedorczyk, Bartłomiej, Mames, Adam, Pietrzak, Mariusz, Puzio, Zuzanna, Szkudlarek, Piotr Grzegorz
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 02-03-2021
• Subjects: Amplification; Catalysts; Epidermal growth factor; Epidermal growth factor receptors; Exchanging; Experiments; Growth factor receptors; Growth factors; Hyperpolarization; Iridium; Ligands; Molecular structure; NMR; NMR spectroscopy; Nuclear magnetic resonance; Peptides; Phenylalanine; Receptors; Resonance; SABRE; Steric hindrance; Substrates; tyrosine kinases; hyperpolarization; epidermal growth factor receptors; NMR spectroscopy; tyrosine kinases; SABRE
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202000711

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 H2 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 1H 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 1H 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.
SABRE hyperpolarization of complex molecules with crucial biological activity: The PyFALGEA oligopeptide is a highly selective ligand towards the tyrosine kinase epidermal growth factor receptor (EGFR). Here, the SABRE hyperpolarization of the PyFALGEA molecule was demonstrated. This research indicated that SABRE can be employed to enhance the NMR signals of very complex biorelevant molecules.