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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

Ana Guerreiro
PhD Student

Bruno L Oliveira
Senior Post-Doctoral Researcher

Bárbara Sousa
PhD Student

Carlos Labão-Almeida
PhD Student

Cláudia Afonso
PhD Student

Inês Albuquerque
PhD Student

João Conde
Post-Doctoral Researcher

João Seixas
Staff Scientist

Marta Marques
Post-Doctoral Researcher

Pedro Cal
Post-Doctoral Researcher

Ravikumar G.
Post-Doctoral Researcher

Tiago Rodrigues
Staff Scientist

Unnikrishnan Vickraman Nair Bindu
PhD Student

Vera Ferreira
PhD Student

Research Areas

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

Ongoing Research Projects

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


  • 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

Selected Publications

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