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Chemical Biology & Pharmaceutical Biotechnology

Our research programme is at the interfaces of Chemistry and Biology. It aims at developing novel chemoselective methods and their use for selective protein/ligand labeling in vitro and in vivo to understand and influence human disease.

Site-selective Protein Modification: At the core of our research programme is the development of efficient chemoselective methods compatible with biological systems and their use to redesign the structure and function of proteins of biological and therapeutic interest.

Synthetic Biologics: Engineered and modified proteins hold great promise for the treatment and prevention of human diseases. Our research group is particularly interested in the specific delivery of toxic molecules to cancer cells and in the construction of homogenous glycoproteins as vaccines candidates.

Delivery of Therapeutic CO: Carbon monoxide-releasing molecules (CO-RMs) have the potential to constitute safe treatments if CO release in vivo can be controlled in a spatial and temporal manner. We are currently investigating the use of carbonyl metalloproteins for the delivery of therapeutic amounts of CO to diseased tissues.

Research Team

Alexandra Isabel Rosa
Project Manager
alexandrarosa@medicina.ulisboa.pt

Ana Guerreiro
PhD Student
anamguerreiro@medicina.ulisboa.pt

Bruno L Oliveira
Senior Postdoctoral Researcher
bruno.oliveira@medicina.ulisboa.pt

Bárbara Sousa
PhD Student
bbsousa@medicina.ulisboa.pt

Carlos Labão-Almeida
PhD Student
carlosalmeida@medicina.ulisboa.pt

Cláudia Afonso
PhD Student
claudiaafonso@medicina.ulisboa.pt

Inês Albuquerque
PhD Student
mialbuquerque@medicina.ulisboa.pt

Luís Miguel Afonso Ramos de Carvalho
Postdoctoral Researcher
luis.carvalho@medicina.ulisboa.pt

Maria Rebelo
Postdoctoral Researcher
mariarebelo@medicina.ulisboa.pt

Marta Marques
Postdoctoral Researcher
martamarques@medicina.ulisboa.pt

Pedro Cal
Postdoctoral Researcher
pcal@medicina.ulisboa.pt

Ravikumar G.
Postdoctoral Researcher
ravikumar.govindan@medicina.ulisboa.pt

Tiago Rodrigues
Staff Scientist
tiago.rodrigues@medicina.ulisboa.pt

Unnikrishnan Vickraman Nair Bindu
PhD Student
unnikrishnan.bindu@medicina.ulisboa.pt

Vera Ferreira
PhD Student
veraferreira@medicina.ulisboa.pt

Research Areas

  • Site-selective protein modification
  • Synthetic biologics
  • Targeted cancer therapeutics
  • Carbohydrate-based vaccines

Ongoing Research Projects

2019/2021 SIMICA: H2020-WIDESPREAD-Twinning (H2020-852985). Site-selective protein-modification chemistries for antibody-drug conjugates (ADCs). Coordinator: Bruno Oliveira. Funding Agency: European Commission.

2018/2021 ACORN: H2020-WIDESPREAD-Twinning (H2020- 807281). Nanoparticle-Based Therapeutic Applications and Detection of Carbon Monoxide Releasing. Coordinator: Tiago Rodrigues. Funding Agency: European Commission.

2018/2021 Intracellular Drug Delivery using Small Molecule Drug Conjugates for Prostate Cancer Therapy. Coordinator: João Seixas. Funding Agency: Fundação para a Ciência e a Tecnologia.

2018/2021 Drug delivery of bioactive agents through selective decaging. Coordinator: Tiago Seixas. Funding Agency: Fundação para a Ciência e a Tecnologia.

Previous Research Projects:

2016/2019 PTDC/QEQ-QOR/1434/2014.

2016/2019 HMSP-ICT/0012/2013.

2015/2019 ProteinConjugates H2020-MSCA-ITN.

2015/2019 GLICOVAX H2020-MSCA-ITN.

2014/2018 Hovione PhD Studentship.

2014/2017 Marie Curie CIG.

Awards

  • 2019 Gonçalo Bernardes. Prémio Prestígio, Associação Física de Torres Vedras, Portugal.
  • 2019 João Seixas. Best Poster Award for his poster communication at the EFMC-ACSMEDI MedChem Frontiers. Krakow, Poland.
  • 2019 Gonçalo Bernardes, João Seixas, Pedro Cal and Tiago Rodrigues. Investment from Portugal Ventures in a spin out of iMM, TargTex Lda. Portugal.
  • 2019 Ana Guerreiro. Best oral communication at the 13th International Meeting of the Portuguese Carbohydrate Group – GLUPOR 13, Porto, Portugal. September.
  • 2018 Gonçalo Bernardes. MedChemComm Emerging Investigator Lectureship.
  • 2016 Gonçalo Bernardes. Harrison-Meldola Memorial Prize – Royal Society of Chemistry.
  • 2016 Gonçalo Bernardes. Chem Soc Rev Emerging Investigator Lectureship.
  • 2016 Gonçalo Bernardes. International Award of the Belgian Society of Pharmaceutical Sciences (BSPS).
  • 2015 Gonçalo Bernardes. 2nd Prize – Royal Society of Chemistry Emerging Technologies Competition 2015 – Health Care.
  • 2015 Gonçalo Bernardes. European Prize of the RSEQ Chemical Biology Division.
  • 2014 Gonçalo Bernardes. European Young Chemist Award (EYCA2014) - Silver Medal.

Selected Publications

From a total of 120 publications – See Google Scholar

120 Stable pyrrole-linked bioconjugates through tetrazine-triggered azanorbornadiene fragmentation. Gil de Montes E; Istrate A; Navo CD; Jiménez-Moreno E; Hoyt EA; Corzana FC; Robina I; Jiménez-Osés G; Moreno-Vargas AJ; Bernardes GJL* Angew. Chem. Int. Ed. 2020, DOI: 10.1002/anie.201914529.

116 Enhancement of the anti-aggregation activity of a molecular chaperone using a rationally designed post-translational modification. Lindstedt PR; Aprile FA; Matos MJ; Perni M; Bertoldo JB; Bernardim B; Peter Q; Jiménez-Osés G; Knowles TPJ; Dobson CM; Corzana F; Vendruscolo M; Bernardes GJL* ACS Cent. Sci. 2019, 5, 1417–1424.

110 Quaternization of vinyl/alkynyl pyridine enables ultrafast cysteine-selective protein modification and charge modulation. Matos MJ; Navo CD; Hakala T; Ferhati X; Guerreiro A; Hartmann D; Bernardim B; Saar KL; Compañón I; Corzana F; Knowles TPJ; Jiménez-Osés G; Bernardes GJL* Angew. Chem. Int. Ed. 2019, 58, 6640–6644.

96 Efficient and irreversible antibody-cysteine bioconjugation using carbonylacrylic reagents. Bernardim B; Matos MJ; Ferhati X; Compañón I; Guerreiro A; Akkapeddi P; Burtoloso ACB; Jiménez-Osés G; Corzana F; Bernardes GJL* Nat. Protoc. 2019, 14, 86–99.

94 Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells. Sun S; Oliveira BL; Jiménez-Osés G; Bernardes GJL* Angew. Chem. Int. Ed. 2018, 57,15832–15835.

93 Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor. Rodrigues T; Werner M; Roth J; da Cruz EHG; Marques MC; Akkapeddi P; Lobo SA; Koeberle A; Corzana F; da Silva Júnior EN; Werz O; Bernardes GJL* Chem. Sci. 2018, 9, 6885–7018. Selected as a Hot Article and as most impactful Chemical Biology articles of 2018. Highlighted in Chemistry World 2018, 26 July 2018 “Artificial intelligence seeks out new anticancer drugs”.

87 A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging. Stenton BJ; Oliveira BL; Matos MJ; Sinatra L; Bernardes GJL* Chem. Sci. 2018, 9, 4185–4189.

86 Chemo and regioselective lysine modification on native proteins. Matos MJ; Oliveira BL; Martínez-Sáez N; Guerreiro A; Cal PMSD; Bertoldo J; Maneiro M; Perkins E; Howard J; Deery MJ; Chalker JM; Corzana F; Jiménez-Osés G; Bernardes GJL* J. Am. Chem. Soc. 2018, 140, 4004–4017. Highlighted in Chem. Eng. News, 2018, 96, 13 “Computer-designed reagent targets lysine for protein modification”; and in Phys.org “How to spark a chemical chain reaction”, 9 March 2018.

78 Chemoselective installation of amine bonds on proteins through aza-Michael ligation. Freedy AM; Matos MJ; Omar Boutureira O; Corzana F; Guerreiro A; Somovilla VJ; Rodrigues T; Nicholls K; Xie B; Jiménez-Osés G; Brindle KM; Neves AA; Bernardes GJL* J. Am. Chem. Soc. 2017, 139, 18365–18375.

76 Oxetane grafts installed site-selectively on native disulfides to enhance protein stability and activity in vivo. Martínez-Saez N; Sun S; Oldrini D; Sormanni P; Boutureira O; Carboni F; Compañón I; Deery MJ; Vendruscolo M; Corzana F; Adamo R; Bernardes GJL* Angew. Chem. Int. Ed. 2017, 47, 14963–14967. Recommended on F1000.

75 Post-expression regioselective mutagenesis reveals a water-bridged cysteine–cysteine redox regulation mechanism in bacterial protein tyrosine phosphatases. Bertoldo JB; Rodrigues T; Dunsmore L; Aprile FA; Marques MC; Rosado L; Boutureira O; Steinbrecher TB; Sherman W; Corzana F; Terenzi H; Bernardes GJL* Chem (Cell Press) 2017, 3, 665–677.

66 Vinyl ether–tetrazine pair for the traceless release of alcohols in cells. Jiménez-Moreno E; Guo Z; Oliveira BL; Albuquerque I; Kitowski A; Guerreiro A; Boutureira O; Rodrigues T; Jiménez-Osés G; Bernardes GJL* Angew. Chem. Int. Ed. 2017, 56, 243–247.

62 A minimal, unstrained S-allyl handle for pretargeting Diels–Alder bioorthogonal labelling in live cells. Oliveira BL; Guo Z; Boutureira O; Guerreiro A; Jiménez-Osés G; Bernardes GJL* Angew. Chem. Int. Ed. 2016, 55, 14683–14687.

61 Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents. Bernardim B; Cal PMSD; Matos MJ; Oliveira BL; Martínez-Sáez N; Albuquerque IS; Corzana F; Burtoloso ACB; Jiménez-Osés G; Bernardes GJL* Nat. Commun. 2016, 7, 13128.

59 Unveiling (–)-Englerin A as a modulator of L-type calcium channels. Rodrigues T; Sieglitz F; Somovilla VJ; Cal PMSD; Galione A; Corzana F; Bernardes GJL* Angew. Chem. Int. Ed. 2016, 55, 11077–11081.

48 Spontaneous CO release from RuII(CO)2-protein complexes in aqueous solution, cells and mice. Ferreira MC; Albuquerque IS; Matak-Vinkovic D; Coelho AC; Carvalho SM; Saraiva LM; Romão CC; Bernardes GJL* Angew. Chem. Int. Ed. 2015, 54, 1172–1175.

Selected Key Reviews:

102 Contemporary approaches to site-selective protein modification. Hoyt EA; Cal PMSD; Oliveira BL; Bernardes GJL* Nat. Rev. Chem. 2019, 3, 147–171.

70 Inverse electron demand Diels–Alder reactions in chemical biology. Oliveira BL; Guo Z.; Bernardes GJL* Chem. Soc. Rev. 2017, 46, 4895–4950.

63 Antibody-drug conjugates:The missing link. Rodrigues T; Bernardes GJL* Nat. Chem. 2016, 8, 1088–1090.

53 Site-selective protein-modification chemistry for basic biology and drug development. Krall N; da Cruz FP; Boutureira O; Bernardes GJL* Nat. Chem. 2016, 8, 103–113.

49 Advances in chemical protein modification. Boutureira O; Bernardes GJL* Chem. Rev. 2015, 115, 2174–2195.

Selected Publications as Co-Senior Author (GBernardes co-workers are underligned):

103 Structure-based design of potent tumor-associated antigens: Modulation of peptide presentation by single-atom O/S or O/Se substitutions at the glycosidic linkage. Compañón I;# Guerreiro A#;….Boutureira O; Peregrina JM; Hurtado-Guerrero R; Fiammengo R; Bernardes GJL*; Corzana F* (*co-senior authors) J. Am. Chem. Soc. 2019, 141, 4063–4072.

101 A fully human anti-IL-7Rα antibody promotes anti-tumor activity against T-cell acute lymphoblastic leucemia. Akkapeddi P; Fragoso R; Hixon JA;....Durum SK; Neri D; Bernardes GJL*; Barata JT* (*co-senior authors) Leukemia 2019, 33, 2155–2168.

98 De novo design of potent and selective mimics of IL-2/IL-15. Silva D-A; Yu S; Ulge U; Spangler JB; Jude KM; Labão-Almeida C#;….Bernardes GJL; Dougan M; Garcia C; Baker D Nature 2019, 565, 186–191. See also, “Designer protein delivers signal of choice” E. Yvonne Jones, Nature 2019, 565, 165–166 & “Researchers redesign a cancer-busting protein—without the side effects” Service RF, Science 2019, Jan. 9.

67 A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages. Pereira MMA; Mahú I; Seixas E;....Cohen P; López M; Bernardes GJL*; Domingos AI* (*co-senior authors) Nat. Commun. 2017, 8, 14967. Highlighted on BBC “Toxin that selectively influences nerve cells in fat tissue – a way to combat obesity?” and as part of the Naked Scientists Science Interviews “The nerve cells that control obesity”.

group leader :
Gonçalo Bernardes