A training network for the chemical site-selective modification of proteins: Preparation of the next-generation of therapeutic chemically-defined protein conjugates

Projektinformationen

ProteinConjugates

ID Finanzhilfevereinbarung: 675007

DOI

10.3030/675007

Projekt abgeschlossen

EK-Unterschriftsdatum 28 Juli 2015

Startdatum 1 November 2015

Enddatum 31 Oktober 2019

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 2 542 771,03

EU-Beitrag

€ 2 542 770,72

Koordiniert durch

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Portugal

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Leistungen

Other (27)

New protein based nanoparticles

The method involves the microfluidic aseembly and the chemical functionalization of proteins.

Summer School

On the topic: The future of project conjugates as therapeutics.

Evaluation of a new vascular targeting ADC

Evaluation of a vascular targeting DM1-antibody L19.

A new anti-MUC1-antibody 4 UR PDE PU 20 The method involves the design of a new anti-MUC1-antibody with high affinity and selectivity for modified MUC1 glycopeptides

The method involves the design of a new anti-MUC1-antibody with high affinity and selectivity for modified MUC1 glycopeptides.

New method for the site-selective cysteine modification

The method involves the site selective installation of boronic acids onto the protein via the formation of stable thioethers with modified styrenes and phenyloxadiazole methylsulfones.

Construction of anti-MUC1-fluorofore conjugate

The method involves the site selective modification of a cysteine residue to incorporate a near infra-red dye.

Evaluation of a new CXR4-bortezobib ADC

In vivo and in vitro evaluation of an CXVR4-borrtezomib ADC

Construction of a new CXCR4-bortezomib ADC

The ADC will be prepared via CXCR4-bortezomib conjugation based on disulfide bridging with salicylhydroxamate.

Project Finish

End of the network programmed activities and research.

Construction of protein-based nanostructures modified with CAIX ligands

The method involves the pre and post-site selective modificatiuon of proteins and their microfluidic assisted nanoparticle synthesis.

A new method for disulfide bridging with boronic acid coordinating handles

The method involves the installation of salicylhydroxamate handles site selectively on disulfide bonds

Construction of lectin based drug delivery systems

The method involves the generation of synthetic lectins that bind to glycos phingolipids.

Vacancies advertisement

Announcements of ProteinConjugates vacancies.

Construction of sillafin based drug delivery systems

The method involves the use of sillafin peptides to mediate delivery of cytotoxic drugs.

New method for the site-selective lysine modification

The method involves the use of 2-carbonylbenzeno BAs as amino blocking group and NHS reagents to append cargo.

Project Kick-off

Meeting with the participation of all network members.

Evaluation of a new homogeneous ADC against HER2

In vivo and in vitro evaluation of a marine cytotoxic drugs conjugated to trastuzumab antibody.

A new GMP manufacturing platform

GMP manufacturing platform for the construction of ADCs.

New method for site-selective tryptophan modification

The method involvs the Pd-(II) catalyzed, norbornene-mediated C−H activation reaction for selective alkylation at the C-2 indole position of Trp and selective formation of Caryl-N bonds at Trp.

Construction of a new DM1-antibody L19 ADC vascular targeting ADC

The ADC will be prepared via DM1-antibody L19 ADC conjugation via trp site selective modification.

Construction of a new Transtuzumab-marine drug ADC

The ADC will be prepared via Transtuzumab-marine drug (PharmaMar) conjugation based on Cys site selective modification.

Construction of a new Transtuzumab-SN38 ADC

The ADC will be prepared via Transtuzumab-SN38 conjugation based on Lys site selective modification.

A new method for the disulphide bridging

The method involves disulphide bridging disulfide bonds with pyridazinediones.

Construction of a new Fab (trastuzumab)-doxoribicin ADC

The ADCs will be prepared via Fab-Dox conjugation via disulfide bridging with pyridazinediones.

Winter School

On the topic: Advanced bioconjugation techniques.

New modified silaffins for drug-delivery based on silica nanoparticles

The method involves the functionalization of silaffins with polyamides at lysine residues.

New modified synthetic lectins

The method involves the functionalization of synthetic lectins which recognize CRDs of cancer cells.

Websites, patent fillings, videos etc. (1)

Website completion

Activation of the ProteinConjugateswebsite.

Veröffentlichungen

Peer reviewed articles (13)

Construction of homogeneous antibody–drug conjugates using site-selective protein chemistry

Autoren: Padma Akkapeddi, Saara-Anne Azizi, Allyson M. Freedy, Pedro M. S. D. Cal, Pedro M. P. Gois, Gonçalo J. L. Bernardes
Veröffentlicht in: Chemical Science, Ausgabe 7/5, 2016, Seite(n) 2954-2963, ISSN 2041-6520
Herausgeber: Royal Society of Chemistry
DOI: 10.1039/c6sc00170j

Oriented attachment of V NAR proteins, via site-selective modification, on PLGA–PEG nanoparticles enhances nanoconjugate performance

Autoren: João C. F. Nogueira, Michelle K. Greene, Daniel A. Richards, Alexander O. Furby, John Steven, Andrew Porter, Caroline Barelle, Christopher J. Scott, Vijay Chudasama
Veröffentlicht in: Chemical Communications, Ausgabe 55/53, 2019, Seite(n) 7671-7674, ISSN 1359-7345
Herausgeber: Royal Society of Chemistry
DOI: 10.1039/c9cc02655j

Rab6-dependent retrograde traffic of LAT controls immune synapse formation and T cell activation

Autoren: Jean-Marie Carpier, Andres E. Zucchetti, Laurence Bataille, Stéphanie Dogniaux, Massiullah Shafaq-Zadah, Sabine Bardin, Marco Lucchino, Mathieu Maurin, Leonel D. Joannas, Joao Gamelas Magalhaes, Ludger Johannes, Thierry Galli, Bruno Goud, Claire Hivroz
Veröffentlicht in: The Journal of Experimental Medicine, Ausgabe 215/4, 2018, Seite(n) 1245-1265, ISSN 0022-1007
Herausgeber: Rockefeller University Press
DOI: 10.1084/jem.20162042

Current Challenges in Delivery and Cytosolic Translocation of Therapeutic RNAs

Autoren: Ludger Johannes, Marco Lucchino
Veröffentlicht in: Nucleic Acid Therapeutics, Ausgabe 28/3, 2018, Seite(n) 178-193, ISSN 2159-3337
Herausgeber: Mary Ann Liebert Inc.
DOI: 10.1089/nat.2017.0716

Silica particles with a quercetin–R5 peptide conjugate are taken up into HT-29 cells and translocate into the nucleus

Autoren: Giorgia Del Favero, Friedrich Bialas, Stephanie Grabher, Anja Wittig, Birgit Bräuer, Dagmar Gerthsen, Cécile Echalier, Meder Kamalov, Doris Marko, Christian F. W. Becker
Veröffentlicht in: Chemical Communications, Ausgabe 55/65, 2019, Seite(n) 9649-9652, ISSN 1359-7345
Herausgeber: Royal Society of Chemistry
DOI: 10.1039/c9cc02215e

Boronic acids as building blocks for the construction of therapeutically useful bioconjugates

Autoren: João P. M. António, Roberto Russo, Cátia Parente Carvalho, Pedro M. S. D. Cal, Pedro M. P. Gois
Veröffentlicht in: Chemical Society Reviews, Ausgabe 48/13, 2019, Seite(n) 3513-3536, ISSN 0306-0012
Herausgeber: Royal Society of Chemistry
DOI: 10.1039/c9cs00184k

A fully human anti-IL-7Rα antibody promotes antitumor activity against T-cell acute lymphoblastic leukemia

Autoren: 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
Veröffentlicht in: Leukemia, Ausgabe 33/9, 2019, Seite(n) 2155-2168, ISSN 0887-6924
Herausgeber: Nature Publishing Group
DOI: 10.1038/s41375-019-0434-8

Natural product–drug conjugates for modulation of TRPV1-expressing tumors

Autoren: Charlotte Baker, Tiago Rodrigues, Bernardo P. de Almeida, Nuno L. Barbosa-Morais, Gonçalo J.L. Bernardes
Veröffentlicht in: Bioorganic & Medicinal Chemistry, Ausgabe 27/12, 2019, Seite(n) 2531-2536, ISSN 0968-0896
Herausgeber: Pergamon Press Ltd.
DOI: 10.1016/j.bmc.2019.03.025​

Sequence Programming with Dynamic Boronic Acid/Catechol Binary Codes

Autoren: Marco Hebel, Andreas Riegger, Maksymilian M. Zegota, Gönül Kizilsavas, Jasmina Gačanin, Michaela Pieszka, Thorsten Lückerath, Jaime A. S. Coelho, Manfred Wagner, Pedro M. P. Gois, David Y. W. Ng, Tanja Weil
Veröffentlicht in: Journal of the American Chemical Society, Ausgabe 141/36, 2019, Seite(n) 14026-14031, ISSN 0002-7863
Herausgeber: American Chemical Society
DOI: 10.1021/jacs.9b03107

“Tag and Modify” Protein Conjugation with Dynamic Covalent Chemistry

Autoren: Maksymilian Marek Zegota, Tao Wang, Christiane Seidler, David Yuen Wah Ng, Seah Ling Kuan, Tanja Weil
Veröffentlicht in: Bioconjugate Chemistry, Ausgabe 29/8, 2018, Seite(n) 2665-2670, ISSN 1043-1802
Herausgeber: American Chemical Society
DOI: 10.1021/acs.bioconjchem.8b00358

Dynamic Core-Shell Bioconjugates for Targeted Protein Delivery and Release

Autoren: Christiane Seidler, Maksymilian Marek Zegota, Marco Raabe, Seah Ling Kuan, David Y. W. Ng, Tanja Weil
Veröffentlicht in: Chemistry - An Asian Journal, Ausgabe 13/22, 2018, Seite(n) 3474-3479, ISSN 1861-4728
Herausgeber: Wiley - V C H Verlag GmbbH & Co.
DOI: 10.1002/asia.201800843

A Microfluidic Co-Flow Route for Human Serum Albumin-drug-nanoparticle assembly

Autoren: Tuuli Hakala, Sarah Davies, Zenon Toprakcioglu, Barbara Bernardim, Gonçalo J. L. Bernardes, Tuomas Knowles
Veröffentlicht in: Chemistry - A European Journal, 2020, ISSN 0947-6539
Herausgeber: John Wiley & Sons Ltd.
DOI: 10.1002/chem.202001146

Multi-scale microporous silica microcapsules from gas-in water-in oil emulsions

Autoren: Zenon Toprakcioglu, Tuuli A. Hakala, Aviad Levin, Christian F. W. Becker, Gonçalo G. L. Bernandes, Tuomas P. J. Knowles
Veröffentlicht in: Soft Matter, Ausgabe 16/12, 2020, Seite(n) 3082-3087, ISSN 1744-683X
Herausgeber: Royal Society of Chemistry
DOI: 10.1039/c9sm02274k

Rechte des geistigen Eigentums

Patent (1)

TRPV2 ANTAGONISTS

Antrags-/Publikationsnummer: 20 18050035
Datum: 2018-09-14
Antragsteller: INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES