Journal article
Formation of peptide-based oligomers in dimethylsulfoxide: identifying the precursor of fibril formation
Soft matter, v 16(33), pp 7860-7868
07 Sep 2020
PMID: 32761042
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The well-studied dipeptide fluorenylmethyloxycarbonyl-di-phenylalanine (FmocFF) forms a rigid hydrogel upon dissolving in dimethylsulfoxide (DMSO) and dilution in H2O. 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 pi-pi stacking between Fmoc-groups is observed above 100 mM. The high(3)J((HHC alpha)-H-N) 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 phi-value ofca.-120 degrees, which corresponds to a parallel beta-sheet type conformation. The(3)J((HHC alpha)-H-N) coupling constant of the C-terminal residue is indicative of a polyproline II (pPII)/beta(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.
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Details
- Title
- Formation of peptide-based oligomers in dimethylsulfoxide: identifying the precursor of fibril formation
- Creators
- Matthew S. Levine - Drexel UniversityMoumita Ghosh - Tel Aviv Univ, Sackler Fac Med, Goldschleger Sch Dent Med, Dept Oral Biol, IL-69978 Tel Aviv, IsraelMorgan Hesser - Drexel UniversityNathan Hennessy - University of SheffieldDavid M. DiGuiseppi - Drexel UniversityLihi Adler-Abramovich - Tel Aviv UniversityReinhard Schweitzer-Stenner - Drexel University
- Publication Details
- Soft matter, v 16(33), pp 7860-7868
- Publisher
- Royal Soc Chemistry
- Number of pages
- 9
- Grant note
- DMR-1707770 / National Science Foundation; National Science Foundation (NSF) 1732/17 / ISRAEL SCIENCE FOUNDATION; Israel Science Foundation DMR-1915781 / REU
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; [Retired Faculty]
- Web of Science ID
- WOS:000562593800017
- Scopus ID
- 2-s2.0-85090072322
- Other Identifier
- 991019167851904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Physical
- Materials Science, Multidisciplinary
- Physics, Multidisciplinary
- Polymer Science