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Journal article
Ordered Aggregates of Fmoc-Diphenylalanine at Alkaline pH as a Precursor of Fibril Formation and Peptide Gelation
The journal of physical chemistry. B, v 129(1), pp 260-272
22 Dec 2024
PMID: 39710982
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Abstract
The ultrashort peptide
-fluorenylmethoxycarbonyl-phenylalanyl-phenylalanine (FmocFF) has been largely investigated due to its ability to self-assemble into fibrils (100 nm-μm scale) that can form a sample-spanning gel network. The initiation of the gelation process requires either a solvent switch (water added to dimethyl sulfoxide) or a pH-switch (alkaline to neutral) protocol, both of which ensure the solubility of the peptide as a necessary step preceding gelation. While the respective gel phases are well understood in structural and material characteristics terms the pregelation conditions are known to a lesser extent. The question we asked is to what extent the gel-forming fibrils are already partially formed, i.e., oligomers or protofibrils. Focusing on the pregelation conditions for the pH-switch method, we investigated the self-assembly of soluble FmocFF aggregates in alkaline pH by UV circular dichroism, IR, vibrational circular dichroism, and
H NMR spectroscopy for different peptide concentrations and more systematically as a function of temperature. The temperature dependence of the UVCD spectra of FmocFF in H
O and D
O revealed a complicated isotope effect that affects the peptide backbone and fluorene conformations in peptide aggregates differently. Moreover, we found that the melting of formed aggregates depends on peptide concentration in a nonmonotonic way. At 20 mM the UVCD data revealed the population of at least two different thermodynamic intermediate states, which seem to differ in terms of the relative arrangement of the fluorene moiety. The IR spectrum of this sample at room temperature indicates an antiparallel β-sheet arrangement, as suggested earlier in the literature. However, we show that this interpretation can only be valid if one invokes a nondispersive redshift of the two amide I' bands in a locally crystalline environment. The respective vibrational circular dichroism spectrum of the amide I' region is consistent with a left-handed helically twisted structure of the formed aggregates. A comparison of our data with spectra of the aqueous gel phase suggests that fibrils in the latter resemble the ones at alkaline pH probed by our experiments.
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Details
- Title
- Ordered Aggregates of Fmoc-Diphenylalanine at Alkaline pH as a Precursor of Fibril Formation and Peptide Gelation
- Creators
- Emily Hughes - Drexel UniversityNichole S O'Neill - Drexel UniversityReinhard Schweitzer-Stenner (Corresponding Author) - Drexel University
- Publication Details
- The journal of physical chemistry. B, v 129(1), pp 260-272
- Publisher
- ACS Publications
- Number of pages
- 13
- Grant note
- Drexel UniversityDepartment of Chemistry of Drexel University
The research described in this paper was financed in part by the Department of Chemistry of Drexel University. E.H. was the recipient of an undergraduate Maryanoff Research fellowship in 2021 when she carried out the work reported in this paper.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemistry
- Web of Science ID
- WOS:001382239700001
- Scopus ID
- 2-s2.0-85212773889
- Other Identifier
- 991022005651304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Physical