Peptide nanotubes channels

The rational synthesis of peptide-based nanotubes by self-assembling of polypeptides into a supramolecular structure was demonstrated. This self-organization leads to peptide nanotubes, having channels of 0.8 nm in diameter and a few hundred nanometer long (68). The connectivity of the proteins in these nanotubes is provided by weak bonds, like hydrogen bonds. These structures benefit from the relative flexibility of the protein backbone, which does not exist in nanotubes of covalently bonded inorganic compounds. 

Ghadiri MR, Granja JR, Buehler LK. Artificial transmembrane ion channels from selfassembling peptide nanotubes. Nature (Lond) 1994 369 301-304. 

As an extension of Ghadiri s study, a 12-residue cyclic peptide, cyclo[(Gln-D-Ala-Glu-D-Ala),], afforded self-assembled nanotube materials having a uniform 13-A tailored pore diameter. Specifically sized tubular nanostructures with channel structures can expect various applications. ... 

Ghadiri, M. R., Granja, J. R., and Buehler, L. K. (1994). Artificial transmembrane ion channels from self-assembling peptide nanotubes. Nature 369, 301-304. 

Hwang et al use the second order cumulant expression to examine the potential of mean force for ion transport in a channel—specifically the transport of Na and ions in a cyclic peptide nanotube in water. They show how the de-solvation of the ions on entering the tube produces a free energy barrier and an attractive interaction between the ions and the functionalised tube provide free energy minimum in the tube. 

Two molecules of the ion-channel-forming peptide gramicidin, which contains alternating L- and D-amino acids, have been shown to form a membrane-spanning P-helix. The alternation of L- and D-amino acids is a feature of a series of cyclic peptides that self-assemble into membrane spanning nanotubes. P-Helices have now also been shown to occur as a structural element in proteins consisting only of L-a-amino acids, viz. in the enzyme pectate lyase. Related to the naturally... 

Peptides consisting exclusively of fS- or y-amino acids (amino acids) have emerged as a promising new class of nonnatural oligomers (foldamers) that are able to fold into well-defined secondary structures [41--47]. So far, three different helical secondary structures and two turn motifs [177-181] as well as a parallel [177,179] and an antiparallel [179,182] sheet structure have been identified by two-dimensional NMR spectroscopy, circular dichroism (CD), and/or X-ray diffraction studies. In addition, cyclo- -tetrapeptides have been found to form nanotubes in the solid state [183] and have been used as transmembrane ion channels [184]. All these studies have demon-... 

The peptide cyclo [(D-Ala- L-Glu- D-Ala- L-Glu)2] with an even number of alternating d- and L-amino acids adopts a flat conformation. This macrocyclic synkinon forms extended stacks in water and vesicle membranes. A contiguous P-sheet in the form of tubules may reach a length of a few hundred nanometers and an inner diameter of about 7-8 A in water (Fig. 9.5.4). The tubules also condense to form bundles of about 100 parallel strands. In lipid bilayers these peptide nanotubes are aligned parallel to the hydrocarbon chain and act as ion channels at their rigid outer surfaces. Their regulation by molecular stoppers, applied potentials, etc. has not been achieved so far (Kim et al., 1998). 

Peptides composed of various coded and noncoded amino acid residues self-assemble to form various types of supramolecular architectures, including supramolecular helices and sheets, nanotubes, nanorods, nanovesicles, and nanofibers. The higher-order self-assembly of supramolecular (3-sheets or supramolecular helices composed of short synthetic acyclic peptides leads to the formation of amyloid-like fibrils. Synthetic cyclic peptides were used in supramolecular chemistry as molecular scaffolding for artificial receptors, so as to host various chiral and achiral ions and other small neutral substrates. Cyclic peptides also self-assemble like their acyclic counterparts to form supramolecular structures, including hollow nanotubes. Self-assembling cyclic peptides can be served as artificial ion channels, and some of them exhibit potential antimicrobial activities against drug-resistant bacteria. 

Clark, T.D. Buehler, L.K. Ghadiri, M.R. Self-assembling cyclic (3 -peptide nanotubes as artificial transmembrane ion channels. J. Am. Chem. Soc. 1998, 120. 651-656. 

Fig. 5 Examples of systems able to form channels in membranes. Left the Ghadiri s self-assembled nanotube formed by cyclopeptides. Right The Voyer s 21 amino acid peptide containing six 21-crown-7 L-phenylalanines. In a membrane, the peptide adopts an a-helical conformation that allows the partial alignment of the macrocycles, one over the other.

Another way to transport ions is to provide them with a polar channel—in cells, a protein pore embedded in the membrane with a lipophilic outer face and a hydrophilic inner face. Artificial mimics of ion chaimels include peptide nanotubes—cyclic peptide molecules designed to stack into cylindrical channels by the suitable placement of hydrogen-bonding groups around their edges (Fig. 

Nanotubes from the rtacking of cyclic peptides Nanotubes from dipepiides Naturally occurring peptide membrane channels Amphiphilic surfactant-like nanotubes... 

A recent development of hybrid systems utilizes cyclic peptides in which (l/ ,3 )-3-aminocyclohexanecarboxylic acid alternates with D-x-amino acids. In such structures, the -methylene moiety of each cyclohexane constitutes a part of the inner surface of the cylinder, creating a partially hydrophobic cavity with an approximate van der Waals internal diameter of 5.4 By adding functional groups to C2, it should be possible to prepare nanotubes with greater selectivity as ion channels, catalysts, or receptors, a possibility that is precluded for a- and jS-nanotubes, because all side chains lie on the exterior of the ensemble. 

The first dipeptide nanotube system was L-Val-L-Ala (VA), which forms crystals with narrow hydrophobic channels (diameter about 5 A) lined by peptide side chains.This structure is conceptually different from those of the cyclic peptides in that the pores are generated from self-assembly of small molecules, which are hydrogen bonded, head-to-tail, into helices (Fig. 3a). The extremely robust three-dimensional hydrogen-bonding scaffold was since observed for a series of other hydro-phobic dipeptides.Pore size can be regulated from 3.3 A (L-Ile-L-Val) to 5.2 A (L-Ala-L-Val) by adjusting the bulk of the hydrophobic side chains. Furthermore, L-Ala-L-Val has pores that can adapt their shapes and sizes to absorb large solvent molecules like 2-butanol. 

Interesting nonlinear optical properties were shown by chiral helicenes (5) forming LB films with larger second-order susceptibility than corresponding racemic structures. Nanotubes based on cyclic peptides were reported to form membranes with ion-selective channels. 

Crystal Growth Mechanisms, p. 364 Dendrimers, p. 432 The Diphenylmethane Moiety, p. 452 Hydrophobic Effects, p. 673 Ion Channels and Their Models, p. 742 Micelles and Vesicles, p. 861 Molecular Switches, p. 917 Molecular-level Machines, p. 937 Nonlinear Optical Materials, p. 973 Peptide Nanotubes, p. 1035 TT-TT Interactions Theory and Scope, p. 1076 Rotaxanes and Pseudorotaxanes, p. 1194 Self-Assembly Definition and Kinetic and Thermodynamic Considerations, p. 1248... 

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