The Cyanopyridine–Aminothiol Click Reaction: Expanding Horizons in Chemical Biology

Abstract

Bioorthogonal reactions hold significant promise for applications in chemical biology. Despite their potential, nitriles have often been overlooked as reactive functional groups for selective bioconjugation. The condensation reaction between cyanopyridines and 1,2-aminothiols stands out as a particularly favorable nitrile modification strategy that proceeds under biocompatible conditions. Cyanopyridines can be seamlessly incorporated into peptides and proteins through both chemical and biotechnological approaches. Similarly, the selective integration of 1,2-aminothiols into peptides and proteins is achievable, leveraging the uniquely reactive N-terminal cysteine functional group.

1 Introduction

2 The Biocompatible Condensation Reaction

3 Peptide Macrocyclisation

4 Orthogonality to Cysteine

5 Combination with Genetic Encoding

6 Conclusion

Key words

click chemistry - bioconjugation - peptides - proteins - bioorthogonal - nitrile - cysteine

Publication History

Received: 09 November 2023

Accepted after revision: 20 November 2023

Accepted Manuscript online:
20 November 2023

Article published online:
15 January 2024

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