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1.D.38 The Cyclic Peptide Nanotube (cPepNT) Family

Ion channels and pores stand out from other possible transport mechanisms due to their high selectivity and efficiency in discriminating and transporting ions or molecules across membrane barriers. Montenegro et al. 2013 have designed artificial ion channel models that exploit the self-assembly of conformationally flat cyclic peptides (CPs) into supramolecular nanotubes. Because of the straightforward synthesis of cyclic peptides and the complete control over the internal diameter and external surface properties of the resulting hollow tubular suprastructure, CPs are good candidates for the fabrication of ion channels. Ion channel activity and selective transport of small molecules by these structures are examples of the great potential that cyclic peptide nanotubes show for the construction of functional artificial transmembrane transporters. 

Amphiphilic alcohols are able to form direct H-bonds with channel water and the tube. Both single and double water bridges with the tube were observed with methanol and ethanol. The different adsorption behaviors of the alcohols and water in the dehydrated cyclic peptide nanotube may lead to the potential application of these peptides as a means of separating alcohols from water (Xu et al. 2016).

The stacking of cyclic peptides is a promising strategy for the preparation of nanotubes (Rodríguez-Vázquez et al. 2014). This strategy allows precise control of the nanotube surface properties and the dimensions of the tube diameter, and the incorporation of 3- aminocycloalkanecarboxylate residues in the nanotube-forming peptides allows control over the internal properties of the supramolecular tube. The cyclic peptides are designed to interact with phospholipid bilayers, and the properties and orientation of the nanotube can be tuned by tailoring the peptide sequence. Hydrophobic peptides form transmembrane pores with a hydrophilic orifice, the nature of which has been exploited to transport ions and small molecules efficiently. These synthetic ion channels are selective for alkali metal ions (Na+, K+ or Cs+) over divalent cations (Ca2+) or anions (Cl-). Selectivity has not yet been achieved within the series of alkali metal ions, for which ion transport rates followed the diffusion rates in water. Amphipathic peptides form nanotubes that lie parallel to the membrane. Nanotube formation takes place on the surfaces of bacterial membranes, making them potential antimicrobial agents (Rodríguez-Vázquez et al. 2014).

Molecular dynamic simulations revealed that molecular charge, size, ability to form H-bonds and channel radius all influence the behaviors of NH4+ and NH3 in the cPepNT (Zhang et al. 2016). Higher electrostatic interactions, more H-bonds, and water-bridges were found in the NH4+ system, resulting in its having higher energy barriers, while NH3 can enter, exit and permeate the channels easily.

References associated with 1.D.38 family:

Montenegro J., Ghadiri MR. and Granja JR. (2013). Ion channel models based on self-assembling cyclic peptide nanotubes. Acc Chem Res. 46(12):2955-65. 23898935
Rodríguez-Vázquez, N., H.L. Ozores, A. Guerra, E. González-Freire, A. Fuertes, M. Panciera, J.M. Priegue, J. Outeiral, J. Montenegro, R. Garcia-Fandino, M. Amorin, and J.R. Granja. (2014). Membrane-targeted self-assembling cyclic peptide nanotubes. Curr Top Med Chem 14: 2647-2661. 25515753
Xu, J., J.F. Fan, M.M. Zhang, P.P. Weng, and H.F. Lin. (2016). Transport properties of simple organic molecules in a transmembrane cyclic peptide nanotube. J Mol Model 22: 107. 27083567
Zhang, M., J. Fan, J. Xu, P. Weng, and H. Lin. (2016). Different transport behaviors of NH4 (+) and NH3 in transmembrane cyclic peptide nanotubes. J Mol Model 22: 233. 27600817