Supramolecular Control over Split-Luciferase Complementation

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2016 Jun 30

PMID 27356091

Citations 21

Authors

Ralph P G Bosmans

Jeroen M Briels

Lech-Gustav Milroy

Tom F A de Greef

Maarten Merkx

Luc Brunsveld

Affiliations

Soon will be listed here.

Abstract

Supramolecular split-enzyme complementation restores enzymatic activity and allows for on-off switching. Split-luciferase fragment pairs were provided with an N-terminal FGG sequence and screened for complementation through host-guest binding to cucurbit[8]uril (Q8). Split-luciferase heterocomplex formation was induced in a Q8 concentration dependent manner, resulting in a 20-fold upregulation of luciferase activity. Supramolecular split-luciferase complementation was fully reversible, as revealed by using two types of Q8 inhibitors. Competition studies with the weak-binding FGG peptide revealed a 300-fold enhanced stability for the formation of the ternary heterocomplex compared to binding of two of the same fragments to Q8. Stochiometric binding by the potent inhibitor memantine could be used for repeated cycling of luciferase activation and deactivation in conjunction with Q8, providing a versatile module for in vitro supramolecular signaling networks.

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