Self-assembling cyclic peptides

Scheme 2. Covalent capture of a self-assembled cyclic peptide dimer using the Grubbs ruthenium catalyst.

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. 

Bong. D.T. Ghadiri. M.R. Self-assembling cyclic peptide cylinders as nuclei for crystal engineering. Angew. Chem. Int. Ed. 2001, 40 (11). 2163-2166. 

Figure 22 Molecular structure of the building blocks, (a) Atomic force microscopy image of reduced cyclic peptide adsorbed on mica, (b) A suggested model for the organization of the self-assembled cyclic peptide within the fibrous material. (Reproduced with permission from Ref. 42. WUey-VCH, 2006.)...

Figure 11.8 Self-assembled cyclic-D,L-a-peptide nanotubes containing NDI as the core, (a) Reversible reduction of the NDIs with sodium dithionate. (b) Self-assembly of the peptide NDI nanotube after reduction reaction via chemical or electrochemical methods.

The self-assembling cyclic D,L-cc-peptide nanotubes described demonstrate high stability on surfaces even after two months exposure to ambient temperature. NDI peptide nanotubes 18 may provide a facile method for the preparation of a new class of synthetic biomaterials [16b, 34a]. Recently Sanders and co-workers demonstrated the formation of amino acid-derived NDI hydrogen-bonded supramo-lecular organic M-helical nanotubes in nonpolar solvents and also in the solid state [34b]. The hydrogen-bonded supramolecular nature of the helical nanotubes was confirmed by the circular dichroism (CD) spectrum in chloroform with the addition of methanol, destruction of the supramolecular nanotubes was observed, due to the capabilities of such an aprotic solvent to compete for hydrogen-bond interactions [34b]. 

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. 

Cyclic peptides, self-assembly of, 24 59-60 Cyclic peroxides, 18 436, 447-448, 459 Cyclic poly(aliphatic disulfide)s, 23 712 Cyclic poly(disulfide)s, available information related to, 23 713 Cyclic polyethers, 12 658 chelating agents, 5 710 Cyclic reforming operations, 25 166 Cyclic sesquiterpenoids, biosynthetic routes to, 24 472 Cyclic siloxanes... 

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. ... 

A different kind of self-assembled nanotubes (Figure 4.12) are spontaneously built from cyclic peptides made up of alternating D- andL-amino acids. As predicted by DeSantis group in the mid 1970s [43], the octapeptide cyc/o-[-(D-Ala-Glu-Z)-Ala-Gln)2] 94 [44a] is approximately planar with NH and C=0 bonds orientated perpendicularly to the mean plane of the macro-ring thus... 

Figure 4.12, Self-assembled nanotube built from cyclic peptides.

Fig. 23. Schematic representation of the transmembrane channel created by the self-assembly of eight cyclic peptides 68. (Reproduced with the permission of Ref. 55)...

Fig. 3. (a) Chemical structure of a synthetic cyclic peptide composed of an alternating sequence of D- and L-amino acids. The side chains of the amino acids have been chosen such that the peripheral functional groups of the flat rings are hydrophobic and allow insertion into lipid bilayers, (b) Proposed structure of a self-assembled transmembrane pore comprised of hydrogen bonded cyclic peptides. The channel is stabilized by hydrogen bonds between the peptide backbones of the individual molecules. These synthetic pores have been demonstrated to form ion channels in lipid bilayers (71). 

Channel-like architectures are formed in the mesophase given by complexes of long chain crown ether derivatives [8.196a,b] and long-chain calixarene derivatives display columnar liquid-crystalline arrangements [8.196c]. Self-assembled tubular structures based on cyclic peptide components have been described [8.186]. 

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