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Department of Chemistry


Dr. Gonçalo Bernardes is a University Lecturer, a Royal Society University Research Fellow & a Fellow of Trinity Hall College, Cambridge.

What we do:

Nature has its own machinery for modifying the structure of proteins. In our research, we’re attempting to mimic this machinery to gain significant therapeutic benefits. We’re engineering chemical reactions that enable us to modify proteins while allowing to choose the precise location in the protein’s structure where we want to install these modifications.

This work has a whole range of applications. For example, we’re currently developing ways of selectively labelling proteins in living cells: this can help us monitor the proteins associated with particular diseases without interfering either with the protein’s structure, function, activity and location or upsetting the cell’s normal functions. Another important potential application for this work is linking cytotoxic drug molecules (molecules that are poisonous to cells) to antibodies and then using the antibody to deliver the drug in a very targeted way to the diseased tissue. This could improve the effectiveness of cancer treatments and reduce their side effects.

These are two examples from among our lines of research that use site-selective and bioorthogonal chemistry to address challenges in biology and medicine. We hope our methods may in future be used in laboratories around the world to help develop new drugs with improved effectiveness and reduced side-effects for some of the most common diseases such as cancer.


We are funded by the Royal Society, by research council grants in both countries (EPSRC and FCT Portugal), and by the EU including through a European Research Council Starting and Proof-of-Concept Grants

For further information on our research and for oportunities, please check our research group website.


Protein engineering through chemical, genetic and computational manipulation.
I Hamachi, GJL Bernardes
– Chemical Society reviews
Modular pore-forming immunotoxins with caged cytotoxicity tailored by directed evolution
NL Mutter, M Soskine, G Huang, IS Albuquerque, GJL Bernardes, G Maglia
– ACS Chemical Biology
Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells
S Sun, BL Oliveira, G Jiménez-Osés, GJL Bernardes
– Angew Chem Int Ed Engl
Posttranslational chemical mutagenesis: to reveal the role of non-catalytic cysteine residues in pathogenic bacterial phosphatases
JB Bertoldo, H Terenzi, S Hüttelmaier, GJL Bernardes
– Biochemistry
Synthesis and Biological Evaluation of Homogenous Thiol-Linked NHC*–Au–Albumin and –Trastuzumab Bioconjugates
MJ Matos, C Labão-Almeida, C Sayers, O Dada, M Tacke, GJL Bernardes
– Chemistry - A European Journal
Site-selective installation of an electrophilic handle on proteins for bioconjugation
B Lee, S Sun, E Jiménez-Moreno, AA Neves, GJL Bernardes
– Bioorganic & Medicinal Chemistry
A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging
BJ Stenton, BL Oliveira, MJ Matos, L Sinatra, GJL Bernardes
– Chemical Science
Chemo- and Regioselective Lysine Modification on Native Proteins
MJ Matos, BL Oliveira, N Martínez-Sáez, A Guerreiro, PMSD Cal, J Bertoldo, M Maneiro, E Perkins, J Howard, MJ Deery, JM Chalker, F Corzana, G Jiménez-Osés, GJL Bernardes
– Journal of the American Chemical Society
A silicon-labelled amino acid suitable for late-stage fluorination and unexpected oxidative cleavage reactions in the preparation of a key intermediate in the Strecker synthesis
KR Scroggie, LJ Alcock, MJ Matos, GJL Bernardes, MV Perkins, JM Chalker
– Peptide Science
Machine intelligence decrypts -lapachone as an allosteric 5-lipoxygenase inhibitor
T Rodrigues, M Werner, J Roth, EHG da Cruz, MC Marques, P Akkapeddi, SA Lobo, A Koeberle, F Corzana, EN da Silva Júnior, O Werz, GJL Bernardes
– Chemical science
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01223 336305

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