End-to-end conformational communication through a synthetic purinergic receptor by ligand-induced helicity switching

Robert A. Brown, Vincent Diemer, Simon J. Webb, Jonathan Clayden

Research output: Contribution to journalArticle (Academic Journal)peer-review

66 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)853-860
Number of pages8
JournalNature Chemistry
Volume5
Issue number10
Early online date15 Sep 2013
DOIs
Publication statusPublished - Oct 2013

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