Self-assembled Cyclic Peptide Research Articles

Self-Assembling Cyclic Peptides: Molecular Dynamics Studies of Dimers in Polar and Nonpolar Solvents

The self-assembly of cyclic D,L-alpha-peptides into hollow nanotubes is a crucial mechanistic step in their application as antibacterial and drug-delivery agents. To understand this process, molecular dynamics (MD) simulations were performed on dimers of cyclic peptides formed from cyclo [(-L-Trp-D-N-MeLeu-)4-]2 and cyclo [(-L-Trp-D-Leu-)4-]2 subunits in nonpolar (nonane) and polar (water) solvent. The dimers were observed to be stable only in nonpolar solvent over the full 10 ns length of the MD trajectory. The behavior of the dimers in different solvents is rationalized in terms of the intersubunit hydrogen bonding, hydrogen bonding with the solvent, and planarity of the rings. It is shown that the phi and psi dihedral angles of a single uncapped ring in nonane lie in the beta-sheet region of the Ramachandran plot, and the ring stays in a flat conformation. Steered MD (SMD) simulations based on Jarzynski's equality were performed to obtain the potential of mean force as a function of the distance between the two rings of the capped dimer in nonane. It is also shown that a single peptide subunit prefers to reside close to the nonane/water interface rather than in bulk solvent because of the amphiphilic character of the peptide ring. The present MD results build the foundation for using MD simulations to study the mechanism of the formation of cyclic peptide nanotubes in lipid bilayers.

Self-Assembly of Cyclic Peptides into Nanotubes and Then into Highly Anisotropic Crystalline Materials This work was supported by FCAR Québec.

C3-symmetrische Lactame in der Röhre: Eigens entworfene starre Macrolactamscheiben ordnen sich über Rückgrat-Rückgrat-Wasserstoffbrücken und Van-der-Waals-Kontakte als Endlosröhren an (siehe Schema). Die Röhren bilden wiederum parallel angeordnete Aggregate aus gleichförmig ausgerichteten Dipolen.

Self-Assembly of Cyclic Peptides into Nanotubes and Then into Highly Anisotropic Crystalline Materials

C3-symmetrische Lactame in der Röhre: Eigens entworfene starre Macrolactamscheiben ordnen sich über Rückgrat-Rückgrat-Wasserstoffbrücken und Van-der-Waals-Kontakte als Endlosröhren an (siehe Schema). Die Röhren bilden wiederum parallel angeordnete Aggregate aus gleichförmig ausgerichteten Dipolen.

Self-Assembly of Cyclic Peptides into Nanotubes and Then into Highly Anisotropic Crystalline Materials This work was supported by FCAR Québec.

C3-symmetric lactams in a tube: Specially designed rigid disc-shaped macrolactams self-assemble as endless tubes by means of backbone–backbone hydrogen bonds and van der Waals contacts (see scheme). All the tubes with very strong dipoles further aggregate in a parallel fashion and all the dipoles are still oriented in the same direction.

Self-Assembling Cyclic Peptide Cylinders as Nuclei for Crystal Engineering

A supramolecular recognition interface is formed through the self-assembly of cyclic D,L-peptides. Phenyl–phenyl interactions direct the solid-state organization of dimeric peptide cyclo[(-L-Phe-D-MeN-Ala-L-hPhe-D-MeN-Ala)2] (1) by forming clusters of edge-to-face contacts between dimers (shown left), which suggests that these peptide scaffolds may be useful subunits for crystal engineering. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Self-Assembling Cyclic Peptide Cylinders as Nuclei for Crystal Engineering

Eine Basis für supramolekulare Erkennung bieten durch Selbstorganisation gebildete cyclische D,L-Peptide: Phenyl-Phenyl-Wechselwirkungen steuern die Organisation des dimeren Peptids cyclo[(-L-Phe-D-MeN-Ala-L-hPhe-D-MeN-Ala)2] 1 im Festkörper durch Bildung mehrfacher Fläche-Fläche-Kontakte zwischen den Dimeren (links gezeigt); somit könnten sich diese Peptidgerüste als Untereinheiten im Kristall-Engineering nutzen lassen.

Self-Assembling Cyclic Peptide Cylinders as Nuclei for Crystal Engineering.

A supramolecular recognition interface is formed through the self-assembly of cyclic D,L-peptides. Phenyl-phenyl interactions direct the solid-state organization of dimeric peptide cyclo[(-L-Phe-D-Me N-Ala-L-hPhe-D-Me N-Ala)2 ] (1) by forming clusters of edge-to-face contacts between dimers (shown left), which suggests that these peptide scaffolds may be useful subunits for crystal engineering.

Diffusion-Limited Size-Selective Ion Sensing Based on SAM-Supported Peptide Nanotubes

An approach for the construction of diffusion-limited size-selective sensors is described based on the self-assembly of cyclic peptides into tubular channels in organosulfur self-assembled monolayers on gold films. An eight-residue cyclic peptide of alternating units of d-Leu and l-Trp amino acid residues was incorporated into monolayers of dodecanethiol and octadecyl sulfide and shown to adopt highly oriented tubular structures under specified adsorption conditions. The structural properties of monolayer-supported peptide nanotubes have been analyzed by grazing angle FTIR spectroscopy and their selective ion transport activities by cyclic voltammetry and impedance spectroscopy.