Conformation and Intermolecular Interactions of SA2 Peptides Self-Assembled into Vesicles

Abstract

Previously we have shown that the recombinantly produced SA2 amphiphilic oligopeptide (Ac-Ala-Ala-ValVal-Leu-Leu-Leu-Trp-Glu-Glu-COOH) self-assembles into nanovesicles (van Hell et al. 2007). In this study, the intermolecular interactions that contribute to the formation of such peptide vesicles are examined. First, analysis of a 3-hydroxyflavone fluorescent probe inserted into the peptide assemblies demonstrated that the peptide self-assembly is based on hydrophobic clustering. The polarity of this hydrophobic microenvironment was comparable to that of negatively charged lipid bilayers. A substantial level of hydration at the hydrophilic-hydrophobic interface was detected, as was further confirmed by tryptophan fluorescence analysis. However, organic solvents such as acetonitrile, tetrahydrofuran, or ethanol could not disrupt SA2 oligopeptide vesicles, whereas these solvents fully disintegrated lipid vesicles. Instead, the SA2 assembly immediately disintegrated in hydrogen breaking solvents such dimethylsulfoxide and dimethylformamide, suggesting the involvement of additional intermolecular interactions via hydrogen bonding. Circular dichroism and Fourier transform infrared spectroscopy excluded well-defined patterns of intramolecular hydrogen bonding and indicated the polyproline type II as the dominant SA2 peptide conformation, which enables intermolecular hydrogen bonding. All-atom computational simulations were used to confirm the presence of such intermolecular hydrogen bonds and degrees of hydration. On the basis of the experimental and computational data presented, we propose a model of an interdigitated peptide assembly that involves intermolecular hydrogen bonding in addition to hydrophobic interactions that stabilize SA2 oligopeptide vesicles.

The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail

“…In agreement with our ssNMR data, modern force fields (AMBER ff99SB-ILDN, 40 GROMOS54a7 41 ) consistently showed stable β-sheet formation, while older versions (AMBER ff99 42 ) yielded spurious α-helical peptides, which explains the outcome of previous computational studies. 43 Accordingly, the GROMOS54a7 force field was used for all following atomistic simulations.…”

Three‐Coordinate Nickel(I) Complexes Stabilised by Six‐, Seven‐ and Eight‐Membered Ring N‐Heterocyclic Carbenes: Synthesis, EPR/DFT Studies and Catalytic Activity

“…These vesicles can entrap a drug payload in their aqueous cavities or in the hydrophobic leaflet of their membranes and thus transport the payload through the blood stream. However, peptide vesicles are rarely reported in literature 4, 5. Here we present vesicles using responsive, purely peptidic amphiphiles, designed to interact specifically with one another.…”

“…The driving force for membrane formation—the segregation in solvophobic blocks—is not strong enough due to insufficient, inhomogeneous hydrophilic and hydrophobic surfaces. Mastrobattista et al5 reported recombinantly produced amphiphilic peptides with an additional conical geometry of the hydrophobic part that directs the self‐assembly towards nanosized vesicles. However the polyproline II (PP II) secondary structure displays the hydrophilic backbone and therefore, the peptide lacks a completely hydrophobic part.…”

Guiding principles for peptide nanotechnology through directed discovery

“…92,101 However, these simulations do reveal the importance of dynamic effects in the assembly process and as such have contributed significantly to the understanding of selfassembled systems. Therefore, in order to use information obtained from atomistic MD simulations in directed discovery endeavours there are two basic approaches: (i) to use a smaller model system (e.g., < 100 peptides) to study how the building blocks interact in a locally realistic environment; 35,89,90,[94][95][96][97][98][99][100]133 or (ii) to create model systems with a presumed structure and test the stability. 46,73,74,134,135…”