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TagIt SIGNED

A Minimal-Tag Bioorthogonal Labelling Approach to Protein Uptake, Traffic and Delivery

Total Cost €

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EC-Contrib. €

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Partnership

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 TagIt project word cloud

Explore the words cloud of the TagIt project. It provides you a very rough idea of what is the project "TagIt" about.

photo    turn    selective    function    amino    inform    describe    intracellular    innate    construction    temporal    cycloaddition    label    encoded    internalisation    cancer    localisation    structure    cells    monitoring    dynamic    small    reaction    inverse    context    disease    progression    electron    conceptually    chemoselective    latter    diels    efficient    size    fluorophore    difficult    fluorescence    former    involve    interfere    labelling    treatment    protein    potentially    offers    constitute    of    lack    proteins    methodology    drug    biology    triggered    demand    22    bioorthogonal    site    receptor    conventional    tagged    fashion    overexpress    generally    trafficking    resolution    spatial    applicable    strategy    acid    perturbation    display    genetically    alder    designed    kinetics    canonical    live    react    probe    first    interdisciplinary    cytokine    coupling    tetrazine    minimal    introduction    cellular    will    reactions    acids    alkene    combines    conjugates    fluorogenic    biological    events    safer    rapid    limited    bearing   

Project "TagIt" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website http://www.gbernardeslab.com
 Total cost 1˙499˙106 €
 EC max contribution 1˙499˙106 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-10-01   to  2021-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 1˙499˙106.00

Map

 Project objective

The ability to probe dynamic cellular events that involve disease-associated proteins is limited, to a large extent, by the lack of development of a strategy that can use small coupling partners to react in chemoselective fashion with rapid kinetics that does not interfere with biological function(s) and localisation. In this application, I describe a conceptually new bioorthogonal-labelling approach that combines the introduction of a minimal non-canonical amino acid with chemoselective reactions, which display rapid kinetics, to label proteins in live cells. The small size of the new alkene-tagged amino acids, which will be genetically encoded, should not interfere with the protein’s innate structure, function(s) or localisation. Site-selective bioorthogonal labelling will be achieved through the use of a new photo-triggered [22] cycloaddition reaction with an alkene-bearing fluorophore and the known inverse-electron-demand Diels-Alder reaction with a fluorogenic tetrazine. Although the former offers potentially improved spatial and temporal resolution, the latter allows for turn-on fluorescence. The proposed new methodology will be applied in the context of a key cytokine involved in cancer progression. The ability to label this cytokine with minimal perturbation of its structure, function(s) and localisation will enable monitoring of its internalisation and intracellular trafficking pathways in cells that overexpress its receptor. In doing so, new insight into cancer biology will be generated that will inform the construction of safer, selective and more efficient protein-drug conjugates for targeted cancer treatment. The concept proposed here is designed to be generally applicable to label and study disease-associated proteins that are difficult to access by means of conventional protein-labelling methods and constitute the first integrated, interdisciplinary approach for the development of protein drug-conjugates.

 Publications

year authors and title journal last update
List of publications.
2019 Enrique Gil de Montes, Ester Jiménez-Moreno, Bruno L. Oliveira, Claudio D. Navo, Pedro M. S. D. Cal, Gonzalo Jiménez-Osés, Inmaculada Robina, Antonio J. Moreno-Vargas, Gonçalo J. L. Bernardes
Azabicyclic vinyl sulfones for residue-specific dual protein labelling
published pages: 4515-4522, ISSN: 2041-6520, DOI: 10.1039/c9sc00125e
Chemical Science 10/16 2019-11-25
2019 Srinivasa Rao Adusumalli, Gonçalo J.L. Bernardes
Ethynylbenziodoxolone Reactivity in Cysteine Bioconjugation
published pages: 1932-1934, ISSN: 2451-9294, DOI: 10.1016/j.chempr.2019.07.014
Chem 5/8 2019-11-25
2017 Allyson M. Freedy, Maria J. Matos, Omar Boutureira, Francisco Corzana, Ana Guerreiro, Padma Akkapeddi, Víctor J. Somovilla, Tiago Rodrigues, Karl Nicholls, Bangwen Xie, Gonzalo Jiménez-Osés, Kevin M. Brindle, André A. Neves, Gonçalo J. L. Bernardes
Chemoselective Installation of Amine Bonds on Proteins through Aza-Michael Ligation
published pages: 18365-18375, ISSN: 0002-7863, DOI: 10.1021/jacs.7b10702
Journal of the American Chemical Society 139/50 2019-07-08
2016 Barbara Bernardim, Pedro M.S.D. Cal, Maria J. Matos, Bruno L. Oliveira, Nuria Martínez-Sáez, Inês S. Albuquerque, Elizabeth Perkins, Francisco Corzana, Antonio C.B. Burtoloso, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes
Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents
published pages: 13128, ISSN: 2041-1723, DOI: 10.1038/ncomms13128
Nature Communications 7 2019-07-08
2019 Maria J. Matos, Claudio D. Navo, Tuuli Hakala, Xhenti Ferhati, Ana Guerreiro, David Hartmann, Barbara Bernardim, Kadi L. Saar, Ismael Compañón, Francisco Corzana, Tuomas P. J. Knowles, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes
Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine-Selective Protein Modification and Charge Modulation
published pages: 6640-6644, ISSN: 1433-7851, DOI: 10.1002/anie.201901405
Angewandte Chemie International Edition 58/20 2019-07-08
2019 Padma Akkapeddi, Rita Fragoso, Julie A. Hixon, Ana Sofia Ramalho, Mariana L. Oliveira, Tânia Carvalho, Andreas Gloger, Mattia Matasci, Francisco Corzana, Scott K. Durum, Dario Neri, Gonçalo J. L. Bernardes, João T. Barata
A fully human anti-IL-7Rα antibody promotes antitumor activity against T-cell acute lymphoblastic leukemia
published pages: , ISSN: 0887-6924, DOI: 10.1038/s41375-019-0434-8
Leukemia 2019-07-08
2016 Bruno L. Oliveira, Zijian Guo, Omar Boutureira, Ana Guerreiro, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes
A Minimal, Unstrained S-Allyl Handle for Pre-Targeting Diels-Alder Bioorthogonal Labeling in Live Cells
published pages: 14683-14687, ISSN: 1433-7851, DOI: 10.1002/anie.201608438
Angewandte Chemie International Edition 55/47 2019-07-08
2018 Maria J. Matos, Bruno L. Oliveira, Nuria Martínez-Sáez, Ana Guerreiro, Pedro M. S. D. Cal, Jean Bertoldo, María Maneiro, Elizabeth Perkins, Julie Howard, Michael J. Deery, Justin M. Chalker, Francisco Corzana, Gonzalo Jiménez-Osés, Gonçalo J. L. Bernardes
Chemo- and Regioselective Lysine Modification on Native Proteins
published pages: 4004-4017, ISSN: 0002-7863, DOI: 10.1021/jacs.7b12874
Journal of the American Chemical Society 140/11 2019-07-08
2017 B. L. Oliveira, Z. Guo, G. J. L. Bernardes
Inverse electron demand Diels–Alder reactions in chemical biology
published pages: 4895-4950, ISSN: 0306-0012, DOI: 10.1039/c7cs00184c
Chemical Society Reviews 46/16 2019-07-08

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