Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones

  • Nat Commun. 2020 Feb 21;11(1):1015. doi: 10.1038/s41467-020-14757-4.
Yingqian Zhang   #  1 ,  Chuanlong Zang   #  1 ,  Guoce An  2 ,  Mengdi Shang  1 ,  Zenghui Cui  1 ,  Gong Chen  1 ,  Zhen Xi  1 ,  Chuanzheng Zhou  3
Affiliations
  • 1. State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, College of Chemistry, Nankai University, Tianjin, 300071, China.
  • 2. Department of Forensic Chemistry, Criminal Investigation Police University of China, Liaoning, Shenyang, 110854, China.
  • 3. State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, College of Chemistry, Nankai University, Tianjin, 300071, China. [email protected].
  • # Contributed equally.
PMID: 32081914 DOI: 10.1038/s41467-020-14757-4
Abstract

Many reagents have been developed for cysteine-specific protein modification. However, few of them allow for multi-functionalization of a single Cys residue and disulfide bridging bioconjugation. Herein, we report 3-bromo-5-methylene pyrrolones (3Br-5MPs) as a simple, robust, and versatile class of reagents for cysteine-specific protein modification. These compounds can be facilely synthesized via a one-pot mild reaction and they show comparable tagging efficiency but higher cysteine specificity than the maleimide counterparts. The addition of cysteine to 3Br-5MPs generates conjugates that are amenable to secondary addition by another thiol or cysteine, making 3Br-5MPs valuable for multi-functionalization of a single cysteine and disulfide bridging bioconjugation. The labeling reaction and subsequent treatments are mild enough to produce stable and active protein conjugates for biological applications.

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