Located in Cambridge,
our laboratory works at
the interface of chemistry
and biology with a focus
on protein chemistry and
targeted cancer therapeutics.
Our new work describing small molecules that degrade genomes of SARS-CoV-2 has been
published in ACS Central Science and highlighted in several media, including Fierce Biotech. This study describes a method to convert RNA binders into degraders, which are utilised to target two RNA structures in the
genome of SARS-CoV-2. These molecular constructs are demonstrated to degrade their targets and
exert anti-SARS-CoV-2 effects in a number of model systems.
Congratulations to Gonçalo, who has been recognised by the European Federation for Medicinal Chemistry and Chemical Biology with the EFMC-WuXi AppTec Award for Excellence in Chemical Biology.
Gonçalo's remarkable research in developing a new strategy for 'hijacking' and degrading RNA, dubbed meCLICK-Seq, is recognised in this award. Full details about the award can be found here.
ABOUT OUR WORK
Nature has produced an intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. At the core of our research and in an attempt to mimic nature, we are engineering reactions that allow for post-expression modification of proteins at selected sites. We use such reactions to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, we are developing strategies for site-selective protein labelling in live cells by combining the introduction of small-sized non-proteinogenic tagged amino acids with very rapid chemoselective reactions. We aim to apply these to label and monitor disease-associated proteins under native conditions without interfere with the protein’s innate structure, function, activity and localisation as well as cellular functions.
Another important aspect of protein modification is for example the conjugation of cytotoxic molecules to antibodies to improve efficacy and reduce side effects of cancer treatments. Gonçalo’s laboratory is engineering new reactions that can be performed site-selectively on native antibodies, i.e. without the need for sequence engineering.
These are two examples among other lines of research in our lab that have in common the use of synthetic aqueous chemistry to address challenges in biology and medicine. Our ultimate goal is to see the widespread use of our findings and methodologies by other laboratories around the world and to directly assist in the design and discovery of new drugs with improved selectivity and efficacy for treating cancer.