Conformation and intermolecular interactions of SA2 peptides self-assembled into vesicles.
Previously we have shown that the recombinantly produced SA2 amphiphilic oligopeptide (Ac-Ala-Ala-Val-Val-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.
van Hell
Albert J
AJ
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Klymchenko
Andrey
A
Burgers
Pepijn P
PP
Moret
Ed E
EE
Jiskoot
Wim
W
Hennink
Wim E
WE
Crommelin
Daan J A
DJ
Mastrobattista
Enrico
E
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005419:Flavonoids / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D049329:Nanostructures / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014364:Tryptophan / Q000737:chemistry
D005419:Flavonoids; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D010455:Peptides; D012997:Solvents; D014364:Tryptophan; C041477:3-hydroxyflavone