Controlled membrane translocation provides a mechanism for signal transduction and amplification.

Transmission and amplification of chemical signals across lipid bilayer membranes is of profound significance in many biological processes, from the development of multicellular organisms to information processing in the nervous system. In biology, membrane-spanning proteins are responsible for the transmission of chemical signals across membranes, and signal transduction is often associated with an amplified signalling cascade. The ability to reproduce such processes in artificial systems has potential applications in sensing, controlled drug delivery and communication between compartments in tissue-like constructs of synthetic vesicles. Here we describe a mechanism for transmitting a chemical signal across a membrane based on the controlled translocation of a synthetic molecular transducer from one side of a lipid bilayer membrane to the other. The controlled molecular motion has been coupled to the activation of a catalyst on the inside of a vesicle, which leads to a signal-amplification process analogous to the biological counterpart.We thank the University of Cambridge Oppenheimer Fund for an Early Career Research Fellowship (M.J.L); the Wiener-Anspach Foundation (FWA) for postdoctoral fellowship (FK) ; and Franziska Kundel and David Klenerman for TIRFM imaging experiments

Binding of organic anions to a macrocyclic alkaloid d-tubocurarine

An alkaloid d-tubocurarine in aqueous solution binds 8-anilino-1-naphthalenesulfonate and anions of substituted benzoic, aliphatic dicarboxylic, and N-acetyl-alpha-amino acids. The binding constants vary from ca. 50 to 3300 M(-1) depending on the anion structure, charge and hydrophobicity. The binding of N-acetyl-alpha-amino acids is enantiospecific

Molecular recognition by natural macrocycles .1. d-tubocurarine as a host molecule for organic anions

The binding of 8-anilino-1-naphthalenesulfonate and 15 anions of substituted benzoic. aliphatic dicarboxylic, and N-acetyl-alpha-amino acids to a macrocyclic alkaloid d-tubocurarine in aqueous solution has been studied by fluorometry, conductometry, and H-1 NMR. The binding constants vary from ca. 50 to 3300 m (1)depending on the guest structure, charge and hydrophobicity. The results of fluorescence and NMR studies show that the host-guest complexation of the anions of aromatic acids involves the formation of a salt bridge between the quaternary nitrogen of the alkaloid and the anionic group of the guest as well as hydrophobic/Van der waals interactions between the guest and host aromatic moieties. The binding of dianions of aliphatic dicarboxylic acids most probably is purely electrostatic. In general, d-tubocurarine possesses binding ability comparable to that of synthetic cyclophanes, It binds enantiospecifically anions of N-acetyl-alpha-amino acids and discriminates between positional isomers of anions of hydroxy and carboxy substituted benzoic acids

Phosphatase-triggered guest release from a cyclodextrin complex

[GRAPHICS] A synthetic supramolecular system is described that models the effect of phosphoryl transfer in molecular recognition. beta-Cyclodextrin-6A-phosphate (pCD), which is shown to be a substrate of alkaline phosphatase, binds cationic aromatic guests, including anticancer agents, up to 100-fold better than native beta-CD. The above observations demonstrate that pCD is capable of releasing the guests from its cavity upon hydrolysis with the phosphatase, as also confirmed by monitoring the hydrolysis in the presence of a guest