End-to-end conformational communication through a synthetic purinergic receptor by ligand-induced helicity switching.
The long-range communication of information, exemplified by signal transduction through membrane-bound receptors, is a central biochemical function. Reversible binding of a messenger ligand induces a local conformational change that is relayed through the receptor, inducing a chemical effect typically several nanometres from the binding site. We report a synthetic receptor mimic that transmits structural information from a boron-based ligand binding site to a spectroscopic reporter located more than 2 nm away. Reversible binding of a diol ligand to the N-terminal binding site induces a screw-sense preference in a helical oligo(aminoisobutyric acid) foldamer, which is relayed to a reporter group at the remote C-terminus, communicating information about the structure and stereochemistry of the ligand. The reversible nature of boronate esterification was exploited to switch the receptor sequentially between left- and right-handed helices, while the exquisite conformational sensitivity of the helical relay allowed the reporter to differentiate even between purine and pyrimidine nucleosides as ligands.
1] School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK [2] Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Robert A
RA
Brown
Vincent
V
Diemer
Simon J
SJ
Webb
Jonathan
J
Clayden
D001897:Boronic Acids / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011485:Protein Binding; D011983:Receptors, Purinergic / Q000737:chemistry*; D012263:Ribonucleosides / Q000737:chemistry
D001897:Boronic Acids; D008024:Ligands; D011983:Receptors, Purinergic; D012263:Ribonucleosides