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Updated: Jun 18, 2026
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Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides
Published on: August 20, 2018
Azide reduction during peptide cleavage from solid support-the choice of thioscavenger?
Philipp E Schneggenburger1, Brigitte Worbs, Ulf Diederichsen
1Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, D-37077 Göttingen, Germany.
Summary
Peptide azides are useful in bioconjugation. This study reveals that peptide azides can be unintentionally reduced to amines during solid-phase peptide synthesis (SPPS) cleavage, depending on the thioscavenger used.
Area of Science:
- Organic Chemistry
- Bioconjugation Chemistry
- Peptide Synthesis
Background:
- Peptide azides are crucial for bioconjugation techniques like click chemistry and Staudinger ligation.
- While methods exist for azide reduction to amines, their occurrence during peptide synthesis cleavage was unobserved.
Purpose of the Study:
- To investigate the reductive transformation of peptide azides during solid-phase peptide synthesis (SPPS) cleavage.
- To determine the influence of thioscavengers on this reductive side reaction.
Main Methods:
- Investigated peptide azide reduction during SPPS cleavage using various thioscavengers.
- Validated the side reaction on azide amino acid building blocks.
- Tested different cleavage cocktails on peptides with varying hydrophobicity and azide positions.
Main Results:
- Observed an extensive side reaction involving the reduction of peptide azides during SPPS cleavage.
- The extent of reduction was dependent on the specific thioscavenger employed.
- The phenomenon was confirmed for both PNA/peptide conjugates and individual azide amino acid building blocks.
Conclusions:
- Peptide azide reduction is a significant side reaction during SPPS cleavage.
- Careful selection of thioscavengers is necessary to prevent unintended azide reduction.
- This finding impacts the synthesis and application of azide-modified peptides and conjugates.
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