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Biologia Química e Biotecnologia Farmacêutica

O programa do meu grupo de investigação situa-se na interface entre a Química e a Biologia. Este programa centra-se no desenvolvimento de novos métodos que permitam a modificação de proteínas e ligandos de um modo específico e cujas condições sejam compatíveis com células e animais. Estes métodos serão a base para esclarecer importantes mecanismos biológicos, e criar uma nova geração de conjugados para o tratamento de cancro e para vacinação.

Modificação selectiva de proteínas: No centro do nosso programa de investigação está o desenvolvimento de métodos quimio-selectivos eficientes, compatíveis com sistemas biológicos e a sua utilização para redesenhar a estrutura e função das proteínas de interesse biológico e terapêutico.

Biologicos sintéticos: as proteínas modificadas são uma grande promessa para o tratamento e prevenção de doenças humanas. O nosso grupo de investigação está particularmente interessado na entrega específica de moléculas tóxicas em células cancerígenas e na construção de glicoproteínas como potenciais vacinas.

Entrega terapêutica de CO: Moléculas libertadoras de monóxido de carbono (CO-RMs) têm o potencial para constituir tratamentos seguros se a libertação CO in vivo ocorrer de forma controlada espacial e temporalmente. Estamos actualmente a investigar o uso de metaloproteínas de carbonilo para a entrega de quantidades terapêuticas de CO em tecidos doentes.

  Informações GLYCOVAX

Equipa de Investigação

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

Vera Ferreira
PhD Student
veraferreira@medicina.ulisboa.pt

Eloah Latocheski
PhD Student
eloah.latocheski@medicina.ulisboa.pt

Rafaela C. Martins
MSc Student
rafaela.martins@medicina.ulisboa.pt

Cong Tang
Project Manager
cong.tang@medicina.ulisboa.pt

Áreas de Investigação

  • Modificação selectiva de proteínas
  • Biológicos sintéticos
  • Terapias selectivas para o tratamento de cancro
  • Glicoproteínas sintéticas para vacinação

Projetos de Investigação em Curso

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

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

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

2018/2021 Drug delivery of bioactive agents through selective decaging. Coordenação: Tiago Seixas. Agência Financiadora: Fundação para a Ciência e a Tecnologia.

Projectos de Investigação Anteriores:

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.

Prémios

  • 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.

Publicações Selecionadas

De um total de 120 publicações – Ver 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