Natural cyclic ionophores valinomycin

Important cation binding systems in Nature are, for example, a class of macro-cyclic compounds termed ionophores and proteins that bind quaternary ammonium ions such as acetylcholine. The ionophores valinomycin 1, nonactin, the ennia-tines, and baeuvericin are cation binders that are structurally quite diverse, yet... 

Crown ethers were the first artificial host molecules discovered. They were accidentally found as a byproduct of an organic reaction. When Pedersen synthesized bisphenol, contaminations from impurities led to the production of a small amount of a cyclic hexaether (Fig. 2.1). This cychc compound increased the solubihty of potassium permanganate in benzene or chloroform. The solubility of this cyclic compound in methanol was enhanced in the presence of sodiiun ion. Based on the observed phenomena, Pedersen proposed that a complex structure was formed where the metal ion was trapped in a cavity created by the cychc ether. At that time, it was already known that naturally occurring ionophores such as valinomycin incorporated specific metal ions to form stable complexes because of this, compounds able to selectively include metal ions were the source of much attention from researchers. Pedersen called the cychc compound a crown ether, because the cychc host wears the ion guest like a crown. 

Various lipophilic natural product antibiotics that have a hydrophobic exterior and a shielded hydrophilic interior capable of binding and transporting ions are known as ionophores. The three ionophores that are most commonly used as probes of ion transport across mitochondrial membranes are the Streptomyces cyclic dodecadepsipeptide valinomycin (57), gramicidin pentadecapeptides (e.g., valine-gramicidin A,... 

Organic ligands that bind to alkali metal and alkaline earth cations are known as ionophores, literally ion carrying compounds. Valinomycin, a cyclic natural antibiotic consisting of alternating d- and L-valine separated by D-hydroxyisovalerate and L-lactate groups shown in Fig. 5.2, binds K+ one thousand times better than... 

The name was coined to describe the activity of compounds. such as valinomycin, a naturally occuning cyclic depsipeptide that transports ions across membranes efficiently and selectively. A number of natural ion transport agents have been identified. They regulate the concentrations of the predominant biological cations (Na", K , Mg, and Artificial ionophores were first... 

Electronic signals in nerve cells travel by means of metal-ion transport laterally in and out of the axon. Such transmembrane transport of ions is fundamental to cell biology, and attempts to mimic it artificially laid the foundation of supramolecular chemistry. Early studies in molecular recognition by Lehn in the 1970s explored the use of crown ethers as mimics of cyclic peptide ionophores like valinomycin, which bind cations selectively in their internal cavities. Natural ionophores act as antibiotics by upsetting the ionic balance across bacterial cell walls. 

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