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Title: Characterization of protein–ligand interactions by SABRE
Nuclear spin hyperpolarization through signal amplification by reversible exchange (SABRE), the non-hydrogenative version of para -hydrogen induced polarization, is demonstrated to enhance sensitivity for the detection of biomacromolecular interactions. A target ligand for the enzyme trypsin includes the binding motif for the protein, and at a distant location a heterocyclic nitrogen atom for interacting with a SABRE polarization transfer catalyst. This molecule, 4-amidinopyridine, is hyperpolarized with 50% para -hydrogen to yield enhancement values ranging from −87 and −34 in the ortho and meta positions of the heterocyclic nitrogen, to −230 and −110, for different solution conditions. Ligand binding is identified by flow-NMR, in a two-step process that separately optimizes the polarization transfer in methanol while detecting the interaction in a predominantly aqueous medium. A single scan Carr–Purcell–Meiboom–Gill (CPMG) experiment identifies binding by the change in R 2 relaxation rate. The SABRE hyperpolarization technique provides a cost effective means to enhance NMR of biological systems, for the identification of protein–ligand interactions and other applications.  more » « less
Award ID(s):
1900406
PAR ID:
10320973
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Chemical Science
Volume:
12
Issue:
39
ISSN:
2041-6520
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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