I saw the sign: An artificial system allows messenger‐induced transmembrane signaling. External addition of a primary messenger molecule (DET, see picture) leads to formation of a heterodimeric complex of transmembrane units bearing tryptophan–dansyl (Trp–Dan) donor–acceptor pairs, which in turn stimulates a strong FRET on the opposite side of the membrane.

The complete, entirely artificial, signal-transduction process was realized with a pair of tailored transmembrane units that were equipped with receptor- and reactive sites at both amphiphilic ends. Thus, docking of the primary messenger, transmission of the signal, and release of the secondary messenger could all be imitated in a single experimental setup. The system imitates the signaling principle of receptor tyrosine kinases and employs bisphosphonate head-groups for oligoamine-recognition and a pair of thiol nucleophiles and pyridine disulfide tail-groups for intravesicle S(N)2 displacement. This system operates in a unidirectional fashion, does not suffer from intervesicle competition, and is highly sensitive towards the lipid composition of the membrane and the nature of the primary messenger.

In einem künstlichen System gelingt die Botenstoff‐induzierte Signalleitung über eine Membran. Die Zugabe des primären Botenstoffs (DET; siehe Bild) führt zur Bildung eines heterodimeren Komplexes aus Transmembran‐Einheiten mit Tryptophan‐Donor (Trp) und Dansyl‐Akzeptor (Dan), der wiederum einen starken FRET‐Effekt auf der Innenseite der Membran induziert (FRET: resonanter Fluoreszenzenergietransfer).

A convergent modular total synthesis is described which affords bisamphiphilic bifunctional transmembrane building blocks useful for artificial signal transduction across membranes. The concept relies on direct Glaser-Hay coupling of lithocholic or cholenic acid propargyl esters, carrying recognition or signaling units on their opposite hydroxy functionalities. For catechol recognition, a 2-(aminomethyl)phenylboronic acid was introduced, while the ammonium alcohol was targeted by a bisphosphonate dianion. Signaling units comprised an N-protected cysteine (thiol nucleophile) and an N-protected cysteine/pyridine disulfide, respectively (disulfide substrate). All these polar headgroups were connected to the hydroxy of the lipid core by ester formation.