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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

Ana Guerreiro
PhD Student
anamguerreiro@medicina.ulisboa.pt

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

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

Gonçalo Bernardes
Group Leader
gbernardes@medicina.ulisboa.pt

Cláudia Afonso
PhD Student
claudiaafonso@medicina.ulisboa.pt

Bárbara Sousa
PhD Student
bbsousa@medicina.ulisboa.pt

Bruno L Oliveira
Senior Post-Doctoral Researcher
bruno.oliveira@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

2014/2017 Pesquisador Visitante Especial, CNPq, Brazil

2014/2017 Marie Curie CIG

2014/2018 Hovione Grant

2013/2018 Investigador FCT - Fundação para a Ciência e a Tecnologia, Portugal

2015/2019 ProteinConjugates H2020-MSCA-ITN

2015/2019 GLICOVAX H2020-MSCA-ITN

2016/2019 PTDC/BBB-BSS/0827/2014

2016/2019 PTDC/QEQ-QOR/1434/2014

Prémios

  • 2016 Harrison-Meldola Memorial Prize – Royal Society of Chemistry
  • 2016 Chem Soc Rev Emerging Investigator Lectureship 2016
  • 2016 International Award of the Belgian Society of Pharmaceutical Sciences (BSPS) 2016
  • 2016 RSC-SAFEA Visiting Researcher Programme – China 2016
  • 2015 2nd Prize – Royal Society of Chemistry Emerging Technologies Competition 2015 – Health Care
  • 2015 European Prize of the RSEQ Chemical Biology Division
  • 2014 European Young Chemist Award (EYCA2014) - Silver Medal
  • 2014 Finalist of the RSC Emerging Technologies Competition 2014
  • 2013 Royal Society of Chemistry/BMOS Young Investigator Award
  • 2013 EFMC Prize for a Young Medicinal Chemist in Academia
  • 2013 Medalha de Serviços Distintos Grau Prata do Ministério da Saúde
  • 2013 Selected for The Lindau Nobel Laureate Meeting
  • 2013 Journals Grant for International Authors, Royal Society of Chemistry
  • 2012 Keystone Symposia Angiogenesis Scholarship
  • 2011 JSP Fellowship of the 46th Bürgenstock Meeting, Brunnen (Switzerland)
  • 2010 OzBio2010 Young Scientist Fellowship, Biochemical Society (UK)
  • 2008 Honorable Mention – European Young Chemistry Award
  • 2007 Poster Highlight Presentation, Gordon Conference Carbohydrates
  • 2006 First Prize in the Pfizer Oxford Organic Chemistry Poster Symposium
  • 2006 Silver Medal for Merit from the Town Hall of Torres Vedras, Portugal
  • 2006 EPA Cephalosporin Scholarship, Linacre College, University of Oxford

Publicações Selecionadas

56. (-)-Englerin A is a L-type calcium channel modulator Rodrigues T; Sieglitz F; Somovilla VJ; Cal PMSD; Galione A; Corzana F; Bernardes GJL* Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201604336

55.  Iminoboronates are efficient intermediates for selective, rapid and reversible N-terminal cysteine functionalisation Faustino H; Silva MJSA; Veiros LF; Bernardes GJL; Gois PMP Chem. Sci. 2016, DOI: 10.1039/C6SC01520D

54. Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents Rodrigues T; Sieglitz F; Bernardes GJL* Chem. Soc. Rev. 2016, DOI: 10.1039/C5CS00916B Emerging Investigators Issue 2016.

53. Construction of Homogeneous Antibody-drug Conjugates using Site-selective Protein Chemistry Akkapeddi P; Azizi S-A; Freedy A; Cal PMSD; Gois PMP; Bernardes GJL* Chem. Sci. 2016, 7, 2954-2963

52. Urban endocrine disruptors targeting breast cancer proteins Montes-Grajales D; Bernardes GJL*; Olivero-Verbel JT Chem. Res. Toxicol. 2016, 29, 150–161

51. Site-selective protein-modification chemistry for basic biology and drug development Krall N; da Cruz FP; Boutureira O; Bernardes GJL* Nature Chem2016, 8, 103–113 Highlighted in Nature Chem 20168, 91 - A little less conjugation, a little more accuracy.

50. Sulfur-Limonene Polysulfide: A Material Synthesized Entirely from Industrial Waste and Its Use in Removing Toxic Metals from Water and Soil Crockett MP; Evans AM; Worthington MJH; Albuquerque IS; Slattery AD; Gibson CT; Bernardes GJL, Chalker JM Angew. Chem. Int. Ed.2016, 55, 1714–1718 Selected as a Hot Paper.

Highlighted in Chemical&Engineering News, November 2, 2015.

49. A N-acetyl cysteine ruthenium tricarbonyl conjugate enables simultaneous release of CO and ablation of ROS species Seixas JD; Chaves-Ferreira M; Montes-Grajales D; Gonçalves AM; Marques AR; Saraiva LM; Olivero-Verbel J; Romão CC; Bernardes GJL* Chem Eur J 2015, Accepted for publication. Selected as a Very Important Paper (VIP).

48. Peptide anchor for folate-targeted liposomal delivery  Nogueira E; Mangialavori IC; Loureiro A; Azoia NG; Sárria MP; Nogueira P; Freitas J; Härmark J; Shimanovich U; Rollett A; Lacroix G; Bernardes GJL, Guebitz GM; Herbert H; Moreira A; Carmo AM; Rossi JPFC; Gomes AC; Preto A; Cavaco-Paulo A Biomacromolecules 2015, DOI:10.1021/acs.biomac.5b00823. 47. Size Controlled Protein Nanoemulsions for Active Targeting of Folate Receptor Positive Cells Loureiro A; Nogueira E; Azoia NG; Sárria MP; Abreu AS; Shimanovich U; Rollet A; Härmark J; Hebert H; Guebitz G;Bernardes GJL; Preto A; Gomes AC; Cavaco-Paulo A Colloids Surf B Biointerfaces 2015135, 90-98.

46. Synthesis of Fluorosugar Reagents for the Construction of Well-Defined Fluoroglycoproteins Salvadó M; Amgarten B; Castillón S; Bernardes GJL*; Boutureira O Org Lett 201517, 2836-2839. 45. X-ray Structures decipher the Non-equivalence of Serine and Threonine O-glycosylation points: Implications for the Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody Martínez-Sáez N; Castro-López J; Valero-González J, Madariaga D; Compañón I; Somovilla VJ; Salvadó M; Asensio JL; Jiménez-Barbero J; Avenoza A; Busto JH; Bernardes GJL; Peregrina JM; Hurtado-Guerrero R; Corzana F Angew Chem Int Ed 2015, DOI: 10.1002/anie.201502813R1.

44. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation Lira-Navarrete E; de las Rivas M; Compañón I; Pallarés MC; Kong Y; Iglesias-Fernández J; Bernardes GJL; Peregrina JM; Rovira C; Bernadó P; Bruscolini P; Clausen H; Lostao A; Corzana F; Hurtado-Guerrero R Nat Commun 20156, 6937.

43. Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice Nogueira E; Lager F; Le Roux D; Nogueira P; Freitas J; Charvet C; Renault G; Loureiro A; Almeida CR; Ohradanova-Repic A; Machacek C; Bernardes GJL; Moreira A; Stockinger H; Burnet M; Carmo AM; Gomes AC; Preto A; Bismuth G; Cavaco-Paulo A J Biomed Nanotechnol 201511, 2243-2252.

42. Folic Acid-Tagged Protein Nanoemulsions Loaded with CORM-2 Enhance the Survival of Mice Bearing Subcutaneous A20 Lymphoma Tumors  Loureiro A; Bernardes GJL*; Shimanovich U; Sárria MP; Nogueira E; Preto A; Gomes AC; Cavaco-Paulo A Nanomedicine 201511, 1077-1183.

41. Histidine-selective metallation in Interleukin-8 with a ruthenium dicarbonyl fragment Albuquerque IS; Jeremias HF; Chaves-Ferreira M; Matak-Vinkovic D; Boutureira O; Romão CC; Bernardes GJL*  Chem Commun 201551, 3993-3996. 40. Advances in chemical protein modification Boutureira O; Bernardes GJL* Chemical Reviews 2015115, 2174–2195.

39. 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 201554, 1172-1175.

38. Collagen labelling with an azide-proline chemical reporter in live cells Amgarten B; Rajan R; Martínez-Sáez N; Oliveira BL; Albuquerque IS; Reid DG; Brooks RA; Duer MJ; Bernardes GJL* Chem Commun 201551, 5250-5252 This manuscript is part of the Emerging Investigators Issue 2015.

37. A contribution to the rational design of Ru(CO)3Cl2L complexes for in vivo delivery of CO Seixas JD; Santos MFA; Mukhopadhyay A; Coelho AC; Reis PM; Veiros LF; Marques AR; Penacho N; Gonçalves AML; Romão MJ; Bernardes GJL; Santos-Silva, T; Romão CC Dalton Trans. 201544, 5058-5075.

36. Functionalized protein nanoemulsions by incorporation of chemically modified BSA Loureiro A; Abreu AS; Sárria MP; Figueiredo MCO; Saraiva LM; Bernardes GJL; Gomes A; Cavaco-Paulo A RSC Adv. 20155, 4976-4983.

35. Highlights from the 49th EUCHEM conference on stereochemistry, Bürgenstock, Switzerland, May 2014 Bernardes GJL*; Lawrence AL Chem. Commun. 201450, 10752-10757.

34. Cysteine Selective Reactions for Antibody Conjugation Cal PMSD; Bernardes GJL*; Gois PMP Angew. Chem. Int. Ed. 201453, 10585-10587.

33. Carbon-monoxide releasing molecules for the delivery of therapeutic CO in vivo García-Gallego, S.; Bernardes, G.J.L.* Angew. Chem. Int. Ed. 201453, 9712-9721. 32. A Small Molecule Drug Conjugate for the Treatment of Carbonic Anhydrase IX Expressing Tumors Krall N; Pretto F; Decurtins W; Bernardes GJL; Supuran CT; Neri D Angew. Chem. Int. Ed. 201453, 4231-4235.

31. Curative Properties of Non-Internalizing Antibody-Drug Conjugates Based on Maytansinoids Perrino E; Steiner M; Krall N; Bernardes GJL; Pretto F; Casi G; Neri D Cancer Research 201474, 2569-2578.

30. Rationally Designed Short Polyisoprenol-linked PglB Substrates for Engineered Polypeptide N-Glycosylation Liu F; Vijayakrishnan B; Faridmoayer A; Taylor TA; Parsons TB; Bernardes GJL; Kowarik M; Davis BG J. Am. Chem. Soc. 201415, 566-569.

29. Protein Micro and Nano Capsules for Biomedical Applications  Shimanovich U; Bernardes GJL*, Knowles TJ; Cavaco-Paulo A Chem. Soc. Rev. 201443, 1361-1371.

28. Site-specific Chemical Modification of Antibody Fragments with Traceless Cleavable Linkers Bernardes GJL; Steiner M; Hartmann I; Neri D; Casi G Nature Protocols 20138, 2079-2089.

27. Highlights from the 48th EUCHEM conference on stereochemistry, Bürgenstock, Switzerland, May 2013 Bernardes GJL* Chem. Commun. 2013, 49, 8578-8582.

26. Synthetically Defined Glycoprotein Vaccines: Current Status & Future Directions Adamo D; Nilo A; Castagner B; Boutureira O; Berti F; Bernardes GJL* Chemical Science 20134, 2995-3008.

25. Spacer Length Shapes Drug Release and Therapeutic Efficacy of Traceless Disulfide-linked ADCs Targeting the Tumor Neovasculature Steiner M; Hartmann I; Perrino E; Casi G; Brighton S; Jelesarov I; Bernardes GJL*; Neri D Chemical Science 20134, 297-302.

24. Generation of Liver Specific Carbon Monoxide-Releasing Molecule (CO-RM) as Drug Candidates for the Treatment of Acute Liver Injury: Targeting of CO-RMs to the Liver Marques AR; Kromer L; Gallo DJ; Penacho NM; Rodrigues SS; Seixas JD; Bernardes GJL; Reis PM; Otterbein SL; Ruggieri RA; Gonçalves ASG; Gonçalves AML; De Matos MN; Bento I; Otterbein LE; Blättler WA; Romão CC Organometallics 201231, 5810-5822. This article is part of the Organometallics in Biology and Medicine special issue.

23. Fucose-specific Conjugation of Hydrazide Derivatives to a Vascular-targeting Monoclonal Antibody in IgG Format Zuberbühler K; Casi G; Bernardes GJL; Neri D Chem. Commun. 201248, 7100-7102.

22. Developing Drug Molecules for Therapy with Carbon Monoxide Romão CC; Seixas JD; Blättler WA; Bernardes GJL* Chem. Soc. Rev. 201241, 3571-3583.

21. A Novel CO-releasing Molecule Fully Protects Mice from Severe Malaria Pena, A.C.; Penacho, N.; Mancio da Silva, L.; Neres, R.; Seixas, J.D.; Fernandes, A.C.; Romão, C.C.; Mota, M.M.;Bernardes, G.J.L.*; Pamplona, A. Antimicrob. Agents Chemother. 201256, 1281-1290. 

20. A Traceless Vascular Targeting Antibody-Drug Conjugate for Cancer Therapy Bernardes GJL; Casi G; Trüssel S; Hartmann I; Schwager K; Scheuermann J; Neri D Angew. Chem. Int. Ed. 201251, 941-944. Selected as a Very Important Paper (VIP). Article highlighted in Chimia 201266, 130; ETH Life – “Starving Cancer”

19. SeS-linked Homogeneous Glycopeptides and Glycoproteins: Synthesis of Human Hepatic ‘Se-Metabolite A' Boutureira O; Bernardes GJL; Fernández-González M; Davis BG Angew. Chem. Int. Ed. 201251, 1432-1436.

18. Direct Radiolabelling of Proteins at Cysteine using [18F]-fluorosugars Boutureira O; Bernardes GJL; D’Hooge F; Davis BG Chem. Commun. 201130, 10010-10012.

17. Towards Improved Therapeutic CORMs: Understanting the Reactivity of CORM-3 with Proteins Santos-Silva T; Mukhopadkyay A; Seixas JD; Bernardes GJL; Romão CR; Romão MJ Curr. Med. Chem. 201118, 3361-3366.

16. Methods for the Conversion of Cysteine to Dehydroalanine on Peptides and Proteins Chalker JM; Gunnoo SB; Boutureira O; Gerstberger SC; Fernández-González M; Bernardes GJL; Griffin L; Hailu H; Schofield CJ; Davis BG Chemical Science 20112, 1666-1676. Article featured on a Cover and highlighted in the Chemical Science Blog.

15. A “Tag-and-Modify” Approach to Site-selective Protein Modification Chalker JM; Bernardes GJL; Davis BG Acc. Chem. Res. 201144, 730-741. This article is part of the Bioorthogonal Chemistry in Biology special issue.

14. Site-selective Traceless Staudinger Ligation for Glycoprotein Synthesis Reveals Scope and Limitations Bernardes GJL; Linderoth L; Doores KJ; Boutureira O; Davis BG ChemBioChem 201112, 1383-1386. Most accessed articles from ChemBioChem in May, June and July 2011.

13. A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates Grayson EJ; Bernardes GJL; Chalker JM; Boutureira O; Koeppe JR; Davis BG Angew. Chem. Int. Ed. 201150, 4127-4132.

12. CORM-3 Reactivity Towards Proteins: The Crystal Structure of a Ru(II) Dicarbonyl-Lysosyme Complex Santos-Silva T; Mukhopadkyay A; Seixas JD; Bernardes GJL*; Romão CR; Romão MJ J. Am. Chem. Soc. 2011133, 1192-1195.

11. Site-selective Chemoenzymatic Construction of Synthetic Glycoproteins using Endoglycosidases Fernández-González M; Boutureira O; Bernardes GJL; Chalker JM; Young MA; Errey JC; Davis BG Chemical Science 20101, 709-715.

10. Design, Synthesis and Biological Evaluation of Carbohydrate-functionalized Cyclodextrins and Liposomes for Hepatocyte-specific Targeting Bernardes GJL; Kikkeri R; Maglinao M; Laurino P; Collot M; Hong SY; Lepenies B; Seeberger PH Org. Biomol. Chem. 20108, 4987-4996. Article highlighted as Hot Article.

9. Fluoroglycoproteins: Ready Chemical Site-selective Incorporation of Fluorosugars into Proteins Boutureira O; D’Hooge F; Fernández-González M; Bernardes GJL; Sánchez-Navarro M; Koeppe JR; Davis BG Chem. Commun. 201046, 8142-8144. Article highlighted as Hot Article and featured on a Cover.

8. Combined Approaches to the Synthesis and Study of Glycoproteins Bernardes GJL; Castagner B; Seeberger PH ACS Chem. Biol. 20094, 703-713. Most accessed articles from ACS Chemical Biology in 2009.

7. Chemical Modification of Proteins at Cysteine: Opportunities in Chemistry and Biology Chalker JM; Bernardes GJL; Lin AY; Davis BG Chem. Asian J. 20094, 630-640. Most accessed articles from Chemistry: An Asian Journal in 2009 and 2010.

6. Allyl Sulfides are Priviliged Substrates in aqueous Olefin Cross-Metathesis: Application to Site-selective Protein Modification Lin AY; Chalker JM; Floyd N; Bernardes GJL; Davis BG J. Am. Chem. Soc. 2008130, 9642-9643.  Article highlighted in: Chemical&Engineering News, July 14, 2008 Nature Chemical Biology 20084, 527-528 Faculty of 1000 Biology

5. Chemical Site-Selective Prenylation of Proteins Gamblin DP; van Kasteren SI; Bernardes GJL; Chalker JM; Oldham NJ; Fairbanks AJ; Davis BG Mol. BioSyst. 20084, 558-561.

4. Facile Conversion of Cysteine and AlkylCysteines to Dehydroalanine: Versatile and Switchable Access to Functionalized Proteins Bernardes GJL; Chalker JM; Errey JC; Davis BG J. Am. Chem. Soc. 2008130, 5052-5053. Article highlighted in: Nature Chemical Biology 20084, 527-528 Chemical&Engineering News, March 31, 2008

3. From Disulfide- to Thioether-linked Glycocoproteins Bernardes GJL; Grayson EJ; Thompson S; Chalker JM; Errey JC; Oualid FE; Claridge TDW; Davis BG Angew. Chem. Int. Ed. 200847, 2244-2247.

2. A Trisulfide-linked Glycoprotein Bernardes GJL; Marston JP; Batsanov AS; Howard JAK; Davis BG Chem. Commun. 2007, 3145-3147.

1. The Direct Formation of Glycosyl Thiols from Reducing Sugars Allows One-pot Protein Glycoconjugation Bernardes GJL; Gamblin DP; Davis BG Angew. Chem. Int. Ed. 200645, 4007-4011.

group leader :
Gonçalo Bernardes