Site-selective tyrosine bioconjugation via photoredox catalysis for native-to-bioorthogonal protein transformation

Li, Beryl X.; Kim, Daniel K.; Bloom, Steven; Huang, Richard Y.-C.; Qiao, Jennifer X.; Ewing, William R.; Oblinsky, Daniel G.; Scholes, Gregory D.; MacMillan, David W. C.

doi:10.1038/s41557-021-00733-y

Site-selective tyrosine bioconjugation via photoredox catalysis for native-to-bioorthogonal protein transformation

Journal Article · Mon Jun 28 00:00:00 UTC 2021 · Nature Chemistry

DOI:https://doi.org/10.1038/s41557-021-00733-y· OSTI ID:1805171

Li, Beryl X. ^[1]; Kim, Daniel K. ^[2]; Bloom, Steven ^[2]; ^[3]; ^[3]; Ewing, William R. ^[3]; ^[2]; ^[2]; ^[2]

Princeton Univ., NJ (United States); Princeton University
Princeton Univ., NJ (United States)
Bristol-Myers Squibb Company, Princeton, NJ (United States)

The growing prevalence of synthetically modified proteins in pharmaceuticals and materials has exposed the need for efficient strategies to enable chemical modifications with high site-selectivity. While genetic engineering can incorporate non-natural amino acids into recombinant proteins, regioselective chemical modification of wild-type proteins remains a challenge. In this work, we use photoredox catalysis to develop a site-selective tyrosine bioconjugation pathway that incorporates bioorthogonal formyl groups, which subsequently allows for the synthesis of structurally defined fluorescent conjugates from native proteins. A water-soluble photocatalyst, lumiflavin, has been shown to induce oxidative coupling between a previously unreported phenoxazine dialdehyde tag and a single tyrosine site, even in the presence of multiple tyrosyl side chains, through the formation of a covalent C–N bond. A variety of native proteins, including those with multiple tyrosines, can successfully undergo both tyrosine-specific and single-site-selective labelling. This technology directly introduces aldehyde moieties onto native proteins, enabling rapid product diversification using an array of well-established bioorthogonal functionalization protocols including the alkyne–azide click reaction.

View Accepted Manuscript (DOE)

Research Organization:: Princeton Univ., NJ (United States)

Sponsoring Organization:: National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division

Grant/Contract Number:: SC0019370

OSTI ID:: 1805171

Journal Information:: Nature Chemistry, Journal Name: Nature Chemistry Vol. 13; ISSN 1755-4330

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (42)

Ligand-Directed Selective Protein Modification Based on Local Single-Electron-Transfer Catalysis Sato, Shinichi; Nakamura, Hiroyuki Angewandte Chemie International Edition, Vol. 52, Issue 33 https://doi.org/10.1002/anie.201303831	journal	July 2013
Systemic Fluorescence Imaging of Zebrafish Glycans with Bioorthogonal Chemistry Agarwal, Paresh; Beahm, Brendan J.; Shieh, Peyton Angewandte Chemie International Edition, Vol. 54, Issue 39 https://doi.org/10.1002/anie.201504249	journal	July 2015
Decarboxylative Peptide Macrocyclization through Photoredox Catalysis McCarver, Stefan J.; Qiao, Jennifer X.; Carpenter, Joseph Angewandte Chemie International Edition, Vol. 56, Issue 3 https://doi.org/10.1002/anie.201608207	journal	November 2016
Divergent Late‐Stage (Hetero)aryl C−H Amination by the Pyridinium Radical Cation Ham, Won Seok; Hillenbrand, Julius; Jacq, Jérôme Angewandte Chemie International Edition, Vol. 58, Issue 2 https://doi.org/10.1002/anie.201810262	journal	January 2019
C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation Garreau, Marion; Le Vaillant, Franck; Waser, Jerome Angewandte Chemie International Edition, Vol. 58, Issue 24 https://doi.org/10.1002/anie.201901922	journal	May 2019
Protein secondary structure analyses from circular dichroism spectroscopy: Methods and reference databases Whitmore, Lee; Wallace, B. A. Biopolymers, Vol. 89, Issue 5, p. 392-400 https://doi.org/10.1002/bip.20853	journal	May 2008
Chemical Protein Modification through Cysteine Gunnoo, Smita B.; Madder, Annemieke ChemBioChem, Vol. 17, Issue 7 https://doi.org/10.1002/cbic.201500667	journal	March 2016
The Phenol‐Phenothiazine Coupling: an Oxidative Click Concept Patureau, Frederic W. ChemCatChem, Vol. 11, Issue 21 https://doi.org/10.1002/cctc.201900152	journal	February 2019
Photocatalytic Modification of Amino Acids, Peptides, and Proteins Bottecchia, Cecilia; Noël, Timothy Chemistry – A European Journal, Vol. 25, Issue 1 https://doi.org/10.1002/chem.201803074	journal	November 2018
Photoluminescence behavior of riboflavin and lumiflavin in liquid solutions and solid films Penzkofer, A. Chemical Physics, Vol. 400 https://doi.org/10.1016/j.chemphys.2012.03.017	journal	May 2012
The Growing and Glowing Toolbox of Fluorescent and Photoactive Proteins Rodriguez, Erik A.; Campbell, Robert E.; Lin, John Y. Trends in Biochemical Sciences, Vol. 42, Issue 2 https://doi.org/10.1016/j.tibs.2016.09.010	journal	February 2017
Residue-Specific Peptide Modification: A Chemist’s Guide deGruyter, Justine N.; Malins, Lara R.; Baran, Phil S. Biochemistry, Vol. 56, Issue 30 https://doi.org/10.1021/acs.biochem.7b00536	journal	July 2017
Tyrosinase-Mediated Bioconjugation. A Versatile Approach to Chimeric Macromolecules Montanari, Elita; Gennari, Arianna; Pelliccia, Maria Bioconjugate Chemistry, Vol. 29, Issue 8 https://doi.org/10.1021/acs.bioconjchem.8b00227	journal	July 2018
Photoredox Catalysis in Organic Chemistry Shaw, Megan H.; Twilton, Jack; MacMillan, David W. C. The Journal of Organic Chemistry, Vol. 81, Issue 16 https://doi.org/10.1021/acs.joc.6b01449	journal	June 2016
On-DNA Decarboxylative Arylation: Merging Photoredox with Nickel Catalysis in Water Kölmel, Dominik K.; Meng, Jiang; Tsai, Mei-Hsuan ACS Combinatorial Science, Vol. 21, Issue 8 https://doi.org/10.1021/acscombsci.9b00076	journal	June 2019
Control of a Tyrosyl Radical Mediated Protein Cross-Linking Reaction by Electrostatic Interaction Minamihata, Kosuke; Goto, Masahiro; Kamiya, Noriho Bioconjugate Chemistry, Vol. 23, Issue 8 https://doi.org/10.1021/bc300137s	journal	July 2012
Facile and Stabile Linkages through Tyrosine: Bioconjugation Strategies with the Tyrosine-Click Reaction Ban, Hitoshi; Nagano, Masanobu; Gavrilyuk, Julia Bioconjugate Chemistry, Vol. 24, Issue 4 https://doi.org/10.1021/bc300665t	journal	March 2013
Proton-Coupled Electron Transfer Weinberg, David R.; Gagliardi, Christopher J.; Hull, Jonathan F. Chemical Reviews, Vol. 112, Issue 7 https://doi.org/10.1021/cr200177j	journal	April 2012
Advances in Chemical Protein Modification Boutureira, Omar; Bernardes, Gonçalo J. L. Chemical Reviews, Vol. 115, Issue 5 https://doi.org/10.1021/cr500399p	journal	February 2015
A Three-Component Mannich-Type Reaction for Selective Tyrosine Bioconjugation Joshi, Neel S.; Whitaker, Leanna R.; Francis, Matthew B. Journal of the American Chemical Society, Vol. 126, Issue 49 https://doi.org/10.1021/ja0439017	journal	December 2004
Transition Metal-Free Tryptophan-Selective Bioconjugation of Proteins Seki, Yohei; Ishiyama, Takashi; Sasaki, Daisuke Journal of the American Chemical Society, Vol. 138, Issue 34 https://doi.org/10.1021/jacs.6b06692	journal	August 2016
Electrochemically Promoted Tyrosine-Click-Chemistry for Protein Labeling Alvarez-Dorta, Dimitri; Thobie-Gautier, Christine; Croyal, Mikael Journal of the American Chemical Society, Vol. 140, Issue 49 https://doi.org/10.1021/jacs.8b09372	journal	November 2018
Water-Soluble Organocatalysts for Hydrazone and Oxime Formation Crisalli, Pete; Kool, Eric T. The Journal of Organic Chemistry, Vol. 78, Issue 3 https://doi.org/10.1021/jo302746p	journal	January 2013
Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials Bloom, Steven; Liu, Chun; Kölmel, Dominik K. Nature Chemistry, Vol. 10, Issue 2 https://doi.org/10.1038/nchem.2888	journal	December 2017
Targeting the N terminus for site-selective protein modification Rosen, Christian B.; Francis, Matthew B. Nature Chemical Biology, Vol. 13, Issue 7 https://doi.org/10.1038/nchembio.2416	journal	June 2017
Choosing an effective protein bioconjugation strategy Stephanopoulos, Nicholas; Francis, Matthew B. Nature Chemical Biology, Vol. 7, Issue 12 https://doi.org/10.1038/nchembio.720	journal	November 2011
Selective chemical protein modification Spicer, Christopher D.; Davis, Benjamin G. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms5740	journal	September 2014
Site-specific chemical protein conjugation using genetically encoded aldehyde tags Rabuka, David; Rush, Jason S.; deHart, Gregory W. Nature Protocols, Vol. 7, Issue 6 https://doi.org/10.1038/nprot.2012.045	journal	May 2012
Fluorescent probes for super-resolution imaging in living cells Fernández-Suárez, Marta; Ting, Alice Y. Nature Reviews Molecular Cell Biology, Vol. 9, Issue 12 https://doi.org/10.1038/nrm2531	journal	November 2008
Practical and regioselective amination of arenes using alkyl amines Ruffoni, Alessandro; Juliá, Fabio; Svejstrup, Thomas D. Nature Chemistry, Vol. 11, Issue 5 https://doi.org/10.1038/s41557-019-0254-5	journal	April 2019
Contemporary approaches to site-selective protein modification Hoyt, Emily A.; Cal, Pedro M. S. D.; Oliveira, Bruno L. Nature Reviews Chemistry, Vol. 3, Issue 3 https://doi.org/10.1038/s41570-019-0079-1	journal	February 2019
A protein functionalization platform based on selective reactions at methionine residues Taylor, Michael T.; Nelson, Jennifer E.; Suero, Marcos G. Nature, Vol. 562, Issue 7728 https://doi.org/10.1038/s41586-018-0608-y	journal	October 2018
Site-selective and versatile aromatic C−H functionalization by thianthrenation Berger, Florian; Plutschack, Matthew B.; Riegger, Julian Nature, Vol. 567, Issue 7747 https://doi.org/10.1038/s41586-019-0982-0	journal	March 2019
Developments and recent advancements in the field of endogenous amino acid selective bond forming reactions for bioconjugation Koniev, Oleksandr; Wagner, Alain Chem. Soc. Rev., Vol. 44, Issue 15 https://doi.org/10.1039/C5CS00048C	journal	January 2015
Electrochemical oxidation induced selective tyrosine bioconjugation for the modification of biomolecules Song, Chunlan; Liu, Kun; Wang, Zhongjie Chemical Science, Vol. 10, Issue 34 https://doi.org/10.1039/C9SC02218J	journal	January 2019
Polarity-reversal catalysis of hydrogen-atom abstraction reactions: concepts and applications in organic chemistry Roberts, Brian P. Chemical Society Reviews, Vol. 28, Issue 1 https://doi.org/10.1039/a804291h	journal	January 1999
The photophysical and photochemical properties of flavins (isoalloxazines) Heelis, P. F. Chemical Society Reviews, Vol. 11, Issue 1 https://doi.org/10.1039/cs9821100015	journal	January 1982
Interaction, thermodynamic, and solubilisation study of amino acid-tyrosine in aqueous anionic and cationic amphiphiles: electrical conductance and spectroscopic studies Malik, Nisar Ahmad; Ali, Anwar Physics and Chemistry of Liquids, Vol. 56, Issue 1 https://doi.org/10.1080/00319104.2017.1292513	journal	February 2017
The Protein Data Bank Berman, H. M. Nucleic Acids Research, Vol. 28, Issue 1 https://doi.org/10.1093/nar/28.1.235	journal	January 2000
Comprehensive analysis of amino acid and nucleotide composition in eukaryotic genomes, comparing genes and pseudogenes Echols, N. Nucleic Acids Research, Vol. 30, Issue 11 https://doi.org/10.1093/nar/30.11.2515	journal	June 2002
Redox-based reagents for chemoselective methionine bioconjugation Lin, Shixian; Yang, Xiaoyu; Jia, Shang Science, Vol. 355, Issue 6325 https://doi.org/10.1126/science.aal3316	journal	February 2017
π-Electronic structure and reactivity of phenoxazine (1), phenothiazine (2), and phenoxthiin (3) Mantsch, H. H.; Dehler, J. Canadian Journal of Chemistry, Vol. 47, Issue 17 https://doi.org/10.1139/v69-523	journal	September 1969

Similar Records

Bioorthogonal catalytic patch

Journal Article · Mon May 10 00:00:00 UTC 2021 · Nature Nanotechnology · OSTI ID:1865095

Euglena mitochondria and chloroplasts form tyrosine-O-sulfate

Journal Article · Sat Apr 01 04:00:00 UTC 1989 · Plant Physiology, Supplement; (USA) · OSTI ID:6611025

Selecting the Right Product: How To's for the Handy Homeowner

Program Document · Thu Jan 05 04:00:00 UTC 2006 · OSTI ID:1218591

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Site-selective tyrosine bioconjugation via photoredox catalysis for native-to-bioorthogonal protein transformation

Citation Formats

References (42)

Similar Records

Related Subjects