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. 2022 Feb 22;12(10):6248-6254.
doi: 10.1039/d1ra08329e. eCollection 2022 Feb 16.

Functionalized quinolizinium-based fluorescent reagents for modification of cysteine-containing peptides and proteins

Karen Ka-Yan Kung  1   2 , Cai-Fung Xu  1 , Wa-Yi O  1   2 , Qiong Yu  1 , Sai-Fung Chung  3 , Suet-Ying Tam  3 , Yun-Chung Leung  3 , Man-Kin Wong  1   2
Affiliations

Functionalized quinolizinium-based fluorescent reagents for modification of cysteine-containing peptides and proteins

Karen Ka-Yan Kung et al. RSC Adv. .

Abstract

A series of quinolizinium-based fluorescent reagents were prepared by visible light-mediated gold-catalyzed cis-difunctionalization between quinolinium diazonium salts and electron-deficient alkyne-linked phenylethynyl trimethylsilanes. The electron-deficient alkynyl group of the quinolizinium-based fluorescent reagents underwent nucleophilic addition reaction with the sulfhydryl group on cysteine-containing peptides and proteins. The quinolizinium-based fluorescent reagents were found to function as highly selective reagents for the modification of cysteine-containing peptides and proteins with good to excellent conversions (up to 99%). Moreover, the modified BCArg mutants bearing cationic quinolizinium compounds 1b, 1d, 1e and 1h exhibit comparable activity in enzymatic and cytotoxicity assays to the unmodified one.

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Conflict of interest statement

M.-K. Wong, K. K.-Y. Kung, Q. Yu and W.-Y. O filed a patent on electron-deficient alkyne-containing quinolizinium compounds (CN113402538A).

Figures

Scheme 1
Scheme 1. (a) Selected examples of organic fluorescent dyes commonly used in bioconjugation reactions. (b) Our design of electron-deficient alkyne-containing quinolizinium compounds for cysteine modification.
Fig. 1
Fig. 1. Chemical structures of quinoliziniums 1a–1h.
See this image and copyright information in PMC

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