Formation of peptide-based oligomers in dimethylsulfoxide: identifying the precursor of fibril formation
The well-studied dipeptide fluorenylmethyloxycarbonyl-di-phenylalanine (FmocFF) forms a rigid hydrogel upon dissolving in dimethylsulfoxide (DMSO) and dilution in H 2 O. Here, we explored the pre-aggregation of the peptide in pure DMSO by vibrational spectroscopies, X-ray powder diffraction and dyna...
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Published in | Soft matter Vol. 16; no. 33; pp. 786 - 7868 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cambridge
Royal Society of Chemistry
26.08.2020
|
Subjects | |
Online Access | Get full text |
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Summary: | The well-studied dipeptide fluorenylmethyloxycarbonyl-di-phenylalanine (FmocFF) forms a rigid hydrogel upon dissolving in dimethylsulfoxide (DMSO) and dilution in H
2
O. Here, we explored the pre-aggregation of the peptide in pure DMSO by vibrational spectroscopies, X-ray powder diffraction and dynamic light scattering. Our results show an equilibrium between a dominant population of amorphous oligomers (on a length scale of 2 nm) and a small number of protofibrils/fibrils (on a length scale of 30 nm in the centimolar and of 200 nm in the sub-molar region). To probe the mechanism underlying the formation of these protofilaments, we measured the
1
H-NMR, IR and visible Raman spectra of DMSO containing different FmocFF concentrations, ranging between 10 and 300 mM. Our data reveal that interpeptide hydrogen bonding leads to the self-assembly of FmocFF in the centimolar region, while π-π stacking between Fmoc-groups is observed above 100 mM. The high
3
J
(H
N
H
Cα
) coupling constant of the N-terminal amide proton indicates that the Fmoc end-cap of the peptide locks the N-terminal residue into a conformational ensemble centered at a
-value of
ca.
−120°, which corresponds to a parallel β-sheet type conformation. The
3
J
(H
N
H
Cα
) coupling constant of the C-terminal residue is indicative of a polyproline II (pPII)/β
t
mixture. Our results suggest that the gelation of FmocFF caused by the addition of a small amount of water to DMSO mixtures is facilitated by the formation of disordered protofibrils in pure DMSO.
The aromatic dipeptide fluorenylmethyloxycarbonyl-di-phenylalanine (FmocFF) self-assembles into amorphous oligomers and fibrils. |
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Bibliography: | Electronic supplementary information (ESI) available: Microscopy images, IR related data, chemical shift temperature dependencies, simulation of amide I VCD and OR profiles, IR spectra of DMSO-water mixtures. See DOI 10.1039/d0sm00035c ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1744-683X 1744-6848 |
DOI: | 10.1039/d0sm00035c |