Entirely Artificial Signal Transduction with a Primary Messenger

Abstract

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.

Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

“…In line with other mechanisms of transduction in cell membranes,w hich require changes in the organization of membrane components and receptor-clustering processes, vesicles have been devised to transmit binding information across their lipid bilayers.O ne example is the use of two different unsymmetrical membrane-spanning transmitter units that in the presence of an external signal molecule can Angewandte Chemie Reviews dimerize,t hus bringing internal signaling groups into close proximity.I nt urn, this approach has led to the possibility of stimulating internal FRET effects [110] to induce metal (i.e.C u 2+ )c omplexation [111] and intramolecular reactions at the inner bilayer surface. [112,113] Schrader and co-workers [113] reported ap air of lithocholic acid based transmembrane blocks functionalized at one end with bisphosphonate dianions for oligoamine recognition and at the other with either at hiol nucleophile or ap yridine disulfide for intravesicle S N 2d isplacement ( Figure 5).…”

Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor

“…2 Cellular signal transduction is largely mediated by three classes of membrane proteins: tyrosine kinase receptors, ligand-gated channels and (most abundantly) G proteincoupled receptors (GPCRs). Efforts have been made to replicate the mode of action of first two, [3][4][5][6] but mimics of GPCRs, which offer the greatest scope for use in synthetic biology, have proved elusive. While many structural details of GPCRmediated signal transduction are poorly understood, 7 a general mechanism is clear.…”

Supramolecular Chemistry in the Biomembrane

“…As an alternative to a chemical output signal, FRET on the intravesicular membrane has also been demonstrated (Figure ) . Therefore, the transmembrane units were synthesized with m ‐xylelene bis‐phosphonate head groups and a tryptophan FRET donor ( 36 ) and a dansyl acceptor ( 37 ) at the other end.…”

“…As an alternative to a chemical output signal, FRET on the intravesicular membrane has also been demonstrated ( Figure 20). [68] Therefore, the transmembrane units were synthesized with m-xylelene bis-phosphonate head groups and a tryptophan FRET donor (36) and a dansyl acceptor (37) at the other end. Incorporation of both transmembrane units into DPPC vesicles gave a moderate FRET signal in the absence of an external messenger, which increased upon the addition of an excess of diethylenetriamine.…”