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Spectroscopy

2D IR indexing maps hIAPP helix-to-sheet kinetics

Maj M, Lomont JP, Rich KL, et al. · Chemical science · 2018

Open access · cc by · source: Europe PMC

Paired 13C18O labels report dihedral angles: monomeric hIAPP is partly helical at L12A13, then oligomers lose helix and fibers form β-sheets.

Study at a glance

Design
Other — 13C18O isotope-edited 2D IR of hIAPP secondary structure during aggregation
N
Biophysical spectroscopy of peptide aggregation — no cohort N
Population
Human islet amyloid polypeptide (hIAPP) monomers/oligomers
Outcome
Site-specific helix vs sheet coupling and aggregation kinetics

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

Helix coupling is +8.3 cm–1 vs +2.5 cm–1 in a β-sheet. Monomers are ~20–38% helical at L12A13; oligomers lack detectable helix; L12A13 shows three-state kinetics unlike two-state A13.

Methodology

Authors 13C18O double-labelled neighbouring residues, calibrated couplings in SDS micelles, and recorded time-resolved 2D IR during aggregation versus singly labelled controls.

Limitations

The leucine-rich-repeat oligomer model is postulated, not a high-resolution oligomer structure; only two labelled sites were tracked.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • Isotope-edited 2D IR can separate helix from sheet at a chosen pair of residues. Neighbouring ¹³C¹⁸O labels give a helix coupling of +8.3 cm⁻¹ versus +2.5 cm⁻¹ in a β-sheet. hIAPP monomers are ~20–38% helical at L12A13; oligomers lack detectable helix; L12A13 shows three-state kinetics unlike two-state A13. Only two labelled sites were tracked; the leucine-rich-repeat oligomer model is postulated, not a high-resolution structure.

    Evidence for the claim as stated.

  • Site-specific 2D IR couplings and a bulk epoxy FTIR trace are not the same vibrational experiment. +8.3 versus +2.5 cm⁻¹ reports secondary structure at L12A13; 906 and 1687 cm⁻¹ report consumption of epoxy and appearance of amide in a thermoset. One is a labelled peptide kinetic; the other is a cure fingerprint. Calling both 'we ran IR' hides that.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

  • Scope difference — different assays, populations, or outcomes

    Site-specific 2D IR couplings and a bulk epoxy FTIR trace are not the same vibrational experiment. +8.3 versus +2.5 cm⁻¹ reports secondary structure at L12A13; 906 and 1687 cm⁻¹ report consumption of epoxy and appearance of amide in a thermoset. One is a labelled peptide kinetic; the other is a cure fingerprint. Calling both 'we ran IR' hides that.

    Also on this tension

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Same topic cluster — not a recommendation engine.