Chemical biology
Protecting-group-free peptide CF3 labeling
Open access · cc by · source: Europe PMC
ZnTFMS/TBHP or Ir photoredox trifluoromethylates tyrosine C–H on unprotected peptides, including insulin, without hitting polar side chains.
Study at a glance
- Design
- Other — Radical CF3 labeling of unprotected peptides and insulin with photoredox or zinc sulfinate conditions
- N
- Peptide chemistry with secondary receptor-binding assays — no subject cohort N
- Population
- Model peptides, hormones, and insulin
- Outcome
- Site-selective tyrosine trifluoromethylation yields and retained insulin activity
Structured fields used in claim comparison tables when every cited study has a complete layer.
Key findings
Photoredox on the Tyr model gave 78% mono-CF3 in MeCN/aqueous AcOH. Asp–Tyr reached 90% combined conversion with 15 mol% Ir and 20 equiv sulfinate; the MSD photoreactor gave 61% combined isolated-scale yield. Insulin was labeled at all four tyrosines (~30% conversion); A19-CF3 insulin was isolated in 12% yield and kept nM insulin-receptor activity (IC50 1.4 vs 0.8 nM).
Methodology
They optimized radical CF3 transfer to Ac-Tyr-NHMe, then dipeptides and longer hormones, using either Zn(SO2CF3)2/TBHP in aqueous acid or NaSO2CF3 plus Ir[dF(CF3)ppy]2(dtbbpy)PF6 under blue light. Insulin was labeled, HPLC-separated, and checked by LC-MS/MS, binding, and NMR.
Limitations
Isolated yields on long peptides are modest; Trp competes when present. The work is labeling chemistry, not an in-cell biological mechanism study. Photoredox scale-up is light-source dependent (Kessil 39% vs MSD 61%).
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.
Preparative HPLC isolates a labelled biomolecule whose conversion on the crude mixture is only modest. Photoredox CF₃ transfer gives 78% mono-CF₃ on Ac-Tyr-NHMe; Asp–Tyr reaches 90% combined conversion; an MSD photoreactor gives 61% combined isolated-scale yield (Kessil 39%). Insulin labelled at all four tyrosines (~30% conversion) afforded A19-CF₃ insulin in 12% isolated yield after HPLC, still with nM insulin-receptor activity. Trp competes when present.
Evidence for the claim as stated.
HPLC as a sequence map, as an activity assay, and as a preparative cut are different jobs. Partial T1 LC–MS aims at >80% mRNA coverage; PDMS–HPLC-fluorescence reports PAH activity (LoQ 0.1–2.5 μM); peptide HPLC isolates 12% yield A19-CF₃ insulin. A student who says 'we ran HPLC' has not said whether the chromatogram is identity, quantity, or a bucket to collect a product.
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.
HPLC as a sequence map, as an activity assay, and as a preparative cut are different jobs. Partial T1 LC–MS aims at >80% mRNA coverage; PDMS–HPLC-fluorescence reports PAH activity (LoQ 0.1–2.5 μM); peptide HPLC isolates 12% yield A19-CF₃ insulin. A student who says 'we ran HPLC' has not said whether the chromatogram is identity, quantity, or a bucket to collect a product.
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