Transmission of Binding Information across Lipid Bilayers

Abstract

A synthetic transmembrane receptor that is capable of transmitting binding information across a lipid bilayer membrane is reported. The binding event is based on aggregation of the receptor triggered by copper(II) complexation to ethylenediamine functionalities. By labelling the receptor with fluorescent dansyl groups, the copper(II) binding event could be monitored by measuring the extent of fluorescence quenching. Comparing the receptor with a control receptor lacking the transmembrane linkage revealed that the transmembrane receptor binds copper(II) ions more tightly than the non-spanning control receptor at low copper(II) concentrations. Since the intrinsic binding to copper(II) is the same for both receptors, this effect was attributed to synergy between the connected interior and exterior binding sides of the transmembrane receptor. Thus, this is the first reported artificial signalling event in which binding of a messenger on one side of the membrane leads to a cooperative binding event on the opposite side of the membrane, resembling biological signalling systems and helping us to get a better understanding of the requirements for more effective artificial signalling systems.

Supramolecular Chemistry in the Biomembrane

“…In a subsequent extension of this work, tail‐to‐tail dimers of cholesterol were equipped with fluorescent dansyl ethylenediamine head groups, which acted as binding sites for copper(II) ions and induced oligomerization of receptor 31 (Figure ) . If Cu 2+ was externally added to vesicles containing the dansylated cholesterol dimers, fluorescence quenching was observed in a Cu 2+ ‐concentration‐dependent manner that was indicative of Cu 2+ binding.…”

Artificial Signal Transduction across Membranes

“…[156] As econd notable design used membrane-spanningc ompounds with protected thiol moieties protruding from the bilayer. [158,159] Although the reported system was responsive to ap rimary messenger,w ith an affinity in the high-micromolar range,t he signalling was not unidirectional across the membrane. Although not triggered by as pecific primary messenger,t his system was the first demonstration of artificial transmembrane signal transduction, where an event on one side of the membrane triggersa reactiono nt he other side.…”

“…This last system illustrates that de novo designed synthetic foldamers can transduce signals by conformational changes, mimicking the working principle of GPCRs, althoughn os econdary messengers were included, neither was signal amplification established. [159] C) The release of thiopyridine as as econdarymessenger after DET-induced receptor oligomerisation completes the receptor cycle of primarym essenger-dimerisation-secondarymessenger. Artificial receptors.A)First artificial bilayer signalling system.…”

Entirely Artificial Signal Transduction with a Primary Messenger

“…In a related area, very few examples of ligand-gated ion channels exist. [10] Some time ago, we developed m-xylylene bisphosphonate dianions as efficient binders for aminoalcohols (such as adrenaline) and especially diammonium cations in aqueous solution. [7] One-side membrane signaling was finally achieved with a lipid signal embedded in a biomembrane model.…”