Artificial ion channels

Studies on artificial ion channels are expected to provide important information on molecular mechanisms and to deepen our understanding of natural ion channels through the establishment of a detailed structure-function relationship. At the same time, the research will contribute to the fascinating area of nanoscale transducers, and may eventually lead to the development of so-called molecular ionics. Here, the author would like to describe the basic concept for the molecular design of various artificial ion channels and to compare their characteristics in the hope of stimulating a future explosion of this research field. Special attention is focused on non-peptidic approaches. Helical bundle approaches " and studies on modified antibiotics " are beyond the scope of this review. 

While the ion pair combination 1 is found to be a successful example to afford artificial ion channels, it may not be difficult to find analogous solutions. Illustrated in Figure 7 is a small expanded scheme for constructing artificial supramolecular ion channels from synthetic amphiphilic pairs of hydrophilic and hydrophobic counterions (note that the combination 2a-2e corresponds to 1). All of these compounds gave stable single-channel currents when incorporated into a bilayer lipid membrane. 

Recently, Ghadiri introduced a brilliant idea for the construction of a new class of artificial ion channels. " He employed an eight-residue 24-membered macro-... 

A cumulative success of artificial ion-channel functions by simple molecules may disclose a wide gate for the design of ion channels and possible applications to ionics devices. Incorporation of these channels into bilayer lipid membrane systems may trigger the developments towards ionics devices. The conventional BLM system, however, is not very stable, one major drawback for the practical applications, and some stabilization methods, such as impregnating the material in micro-porous polycarbonate or polyester filters, are required. On the other hand,... 

Before concluding this review, it is appropriate to comment on estimation methods of artificial ion channels. As described in each experimental method, both planar and liposomal membranes could be used for detecting the ion transport via the channel mechanism. For estimating the ion transport rate across the liposomal membrane, a variety of methodologies have been employed. These may be summarized as follows ... 

Along these lines, supramolecular, bimolecular, as well as unimolecular approaches successfully mimicked the function of natural ion channels by using completely artificial and very simple molecules. Ion fluxes satisfied several criteria that these molecules form ion channels embedded in the bilayer lipid membrane. Non-peptidic artificial ion channels as well as helical bundles are now in our hands and it is likely that many more will soon emerge. The biological importance of these molecules may attract interest from many diverse branches of science—neurobiology, clinical medicine, biophysics, membrane technology, materials science, and others. 

More relevant for this section is the use of porphyrins as template for the construction of de novo metalloproteins. Indeed, the attachment of helical peptide units to these templates creates four-helix bundle structures that have been used as an artificial ion channel 2 or a hydroxylase enzymeJ33,34 In these cases, the peptide units were coupled to the template by using the HOSu or the TBTU methods. As illustrated in Scheme 10 starting from 33, formation of the tetrasuccimidyl ester 34 and attachment of the protected peptide unit 35 gives 36 and this is followed by deprotection to 37. 

Ion channel proteins are large and complex membrane proteins that regulate the flow of ions across cell membranes [52], Since they are associated with several diseases, major efforts have been devoted to the preparation of functional artificial ion channels [53], The challenge here is to design simple... 

Along the same lines, an artificial ion channel was prepared by Montal and coworkers [33] using the TASP approach. In their work, a four a-helix bundle structure 67 was synthesized on a peptide template. The ion transport ability was well characterized and 67 turned out to have several similarities with the natural acetylcholine receptor channel they were mimicking. 

Fig. 22. DeGrado s concept for the development of artificial ion channels. The self-assemblage in a bilayer membrane of an amphiphilic peptide unit generates a hydrophobic oi-helix bundle structure with a polar channel in the middle...

Finally, our approach to the development of artificial ion channels is based on the alignment of six crown ethers attached to an a-helical peptidic nanostructure (69) (Fig. 24) [53,57]. Preliminary results demonstrated that 69 adopts the... 

Several types of studies directed towards the development of artificial ion channels and the understanding of ion motion in channels are being carried out. These effectors will be considered in Section 8.4 they deserve and will receive increased attention, in view also of their potential role as molecular ionic devices. 

Approaches to artificial ion channels have, for instance, made use of macrocyclic units [6.72,6.74] (see also below), of peptide [8.183-8.185] and cyclic peptide [8.186] components, of non-peptidic polymers [8.187] and of various amphiphilic molecules [6.11, 8.188, 8.189]. The properties of such molecules incorporated in bilayer membranes may be studied by techniques such as ion conductance [6.69], patch-clamp [8.190] or NMR [8.191, 8.192] measurements. However, the nature of the superstructure formed and the mechanism of ion passage (carrier, channel, pore, defect) are difficult to determine and often remain a matter of conjecture. 

Hall, C. D. Kirkovits, G. J. Hall, A. C., (1999) Towards a redox-active artificial ion channel Chem. Commun. 1897-1898. 

Roks, M. F. M. Nolte, R. J. M., (1992) Biomimetic macromolecular chemistry design and synthesis of an artificial ion channel based on a polymer containing cofacially stacked crown ether rings. Incorporation in dihexadecyl phosphate vesicles and study of cobalt ion transport Macromolecules 25, 5398-5407. 

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