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

Abstract

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.

Parahydrogen‐Induced Polarization of Amino Acids

“…[7] Thesubstrate scope of SABRE has,therefore, been most commonly illustrated for molecules with N-donor sites that readily ligate to the iridium center. This approach has been extended to pyridine-tagged biocompatible molecular frameworks,i ncluding oligopeptides [100,101] and glycine. [102] SABRE can involve high symmetry catalysts such as [Ir(H) 2 (IMes)(py) 3 ]Cl with chemically equivalent hydride ligands.T heir magnetic inequivalence is responsible for polarization flow.…”

Parawasserstoff‐induzierte Polarisation von Aminosäuren

“…[7] SABRE wurde daher am häufigsten für Moleküle mit N-Donorstellen veranschaulicht, die leicht an Iridium ligieren. Dieser Ansatz wurde auf Pyridin-markierte biokompatible molekulare Gerüste erweitert, darunter Oligopeptide [100,101] und Glycin. [102] SABRE kann hochsymmetrische Katalysatoren wie [Ir(H) 2 (IMes)(py) 3 ]Cl mit chemisch äquivalenten Hydridliganden beinhalten.…”

Optimizing the Reaction Conditions for the Formation of Fumarate via Trans-Hydrogenation

“…PHIP experiments were successfully employed for the detailed investigation of mechanistic problems in organic and inorganic synthesis [19][20][21], for monitoring chemical processes in microreactors, [22][23][24] in time-domain detected experiments [25,26], or in field-cycling [27,28] and ultra-low-field NMR experiments [29][30][31]. They were employed for hyperpolarization of amino acids and peptides [32][33][34][35][36][37][38] and in MRI [39][40][41][42][43][44][45][46][47]. To prolong the application window of PHIP, which is limited by the lifetime of the hyperpolarization, it is advantageous to transfer the hyperpolarization from the hyperpolarized protons to spin-1/2 X-nuclei such as 13 C. Glöggler et al [48,49] reported a pulsed experiment, which can nearly completely transfer the hyperpolarization from the protons to the 13 C. The Side Arm Hydrogenation (PHIP-SAH) 50,51 protocol greatly expanded the range of PHIPpolarizable molecules, which allowed for the hyperpolarization and subsequent in vivo detection of 13 C-labeled pyruvate and its metabolic product lactate in a 1T MRI scanner [52].…”