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Publication . Article . Other literature type . 2019

“Doubly Orthogonal” Labeling of Peptides and Proteins

Romain Tessier; Javier Ceballos; Nora Guidotti; Raphael Simonet-Davin; Beat Fierz; Jerome Waser;
Open Access
Published: 14 Jun 2019 Journal: Chem, volume 5, pages 2,243-2,263 (issn: 2451-9294, Copyright policy )
Publisher: Elsevier BV
Country: Switzerland
Abstract

Summary Herein, we report a cysteine bioconjugation methodology for the introduction of hypervalent iodine compounds onto biomolecules. Ethynylbenziodoxolones (EBXs) engage thiols in small organic molecules and cysteine-containing peptides and proteins in a fast and selective addition onto the alkynyl triple bond, resulting in stable vinylbenziodoxolone hypervalent iodine conjugates. The conjugation occurs at room temperature in an open flask under physiological conditions. The use of an azide-bearing EBX reagent enables a “doubly orthogonal” functionalization of the bioconjugate via strain-release-driven cycloaddition and Suzuki-Miyaura cross-coupling of the vinyl hypervalent iodine bond. We successfully applied the methodology on relevant and complex biomolecules, such as histone proteins. Through single-molecule experiments, we illustrated the potential of this doubly reactive bioconjugate by introducing a triplet-state quencher close to a fluorophore, which extended its lifetime by suppressing photobleaching. This work is therefore expected to find broad applications for peptide and protein functionalization.

Subjects by Vocabulary

Microsoft Academic Graph classification: Chemical biology Hypervalent molecule Fluorophore chemistry.chemical_compound chemistry Small molecule Triple bond Combinatorial chemistry Bioconjugation Biomolecule chemistry.chemical_classification Photobleaching

Subjects

Materials Chemistry, Biochemistry (medical), General Chemical Engineering, Environmental Chemistry, Biochemistry, General Chemistry, hypervalent iodine reagents, in-vivo, next-generation, small molecules, cysteine, palladium, chemistry, bioconjugation, alkynylation, thiols

Funded by
EC| SeleCHEM
Project
SeleCHEM
Overcoming the Selectivity Challenge in Chemistry and Chemical Biology via Innovative Tethering Strategies
  • Funder: European Commission (EC)
  • Project Code: 771170
  • Funding stream: H2020 | ERC | ERC-COG
Validated by funder
,
EC| SeleCHEM
Project
SeleCHEM
Overcoming the Selectivity Challenge in Chemistry and Chemical Biology via Innovative Tethering Strategies
  • Funder: European Commission (EC)
  • Project Code: 771170
  • Funding stream: H2020 | ERC | ERC-COG
Validated by funder
moresidebar