Issue 16, 2024

Fluorescent carbazole-derived α-amino acids: structural mimics of tryptophan

Abstract

Fluorescent tags are commonly used for imaging of proteins and peptides during biological events; however, the large size of dyes can disrupt protein structure and function, and typically require the use of a chemical spacer. Herein, we report the synthesis of a new class of fluorescent unnatural α-amino acid, containing carbazole side-chains designed to mimic L-tryptophan and thus, readily incorporated into peptides. The amino acids were constructed using a Negishi cross-coupling reaction as the key step and exhibited strong fluorescent emission, with high quantum yields in both organic solvents and water. Compatible with solid phase peptide synthesis, the carbazole amino acids were used to replace tryptophan in a β-hairpin model peptide and shown to be a close structural mimic with retention of conformation. They were also found to be effective fluorescent molecular reporters for biological events. Incorporation into a proline-rich ligand of the WW domain protein demonstrated that the fluorescent properties of a carbazole amino acid could be used to measure the protein–protein binding interaction of this important biological signalling process.

Graphical abstract: Fluorescent carbazole-derived α-amino acids: structural mimics of tryptophan

Supplementary files

Article information

Article type
Edge Article
Submitted
19 Feb 2024
Accepted
20 Mar 2024
First published
21 Mar 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2024,15, 5944-5949

Fluorescent carbazole-derived α-amino acids: structural mimics of tryptophan

R. Clarke, L. Zeng, B. C. Atkinson, M. Kadodwala, A. R. Thomson and A. Sutherland, Chem. Sci., 2024, 15, 5944 DOI: 10.1039/D4SC01173B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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