The Institute of Chemical Research of Catalonia (ICIQ), a BIST Community centre, and the Girona Biomedical Research Institute (IDIBGI) have been collaborating since September 2022. Their aim, which has been to explore new therapeutic targets and develop new drugs for cancer treatment, has now led to the development of one of ICIQ’s strategic projects.
ICIQ researchers from left to right: Dr. Ivana Lapuh, Dr. Mª Ángeles Sarmentero, Dr. Félix Cuevas, Dr. Dani Font, and Dr. Fernando Bravo
IDIBGI researchers from left to right: Dr. Jordi Frigola, Marina Guerrero, Adrián Pérez, Lucía Márquez, and Alba Bermejo
The collaboration between ICIQ and IDIBGI harnesses the complementary expertise and knowledge of both institutions to address a significant health issue, namely cancer, from a completely new scientific perspective. This new approach aims to improve the quality of life for people with cancer, strengthening both institutions’ commitment to applying the latest scientific advances to enhance the health of our population.
The project led by Dr. Jordi Frigola, head of the Chromosomal Replication group at IDIBGI, aims to develop new selective inhibitors of the early stages of DNA replication. This is a step that occurs before the cell divides and therefore, stopping it would prevent tumour proliferation. This approach is innovative because it focuses on the early stages of DNA replication, unlike current treatments that target more advanced stages. This new approach opens possibilities for developing more specific treatments with fewer side effects and less toxicity for patients.
In recent years, Dr. Frigola’s group has identified new candidate therapeutic targets for designing and developing specific inhibitors of genomic synthesis. Using these new targets, the ICIQ team is pursuing two complementary approaches to find molecules capable of inhibiting the early stages of DNA replication. “The multidisciplinary collaboration between IDIBGI and ICIQ is giving a significant boost to our research line. The results obtained so far have allowed us to validate our hypothesis, which we have been investigating in Girona for years”, states Dr. Frigola, adding that, “these results indicate that we are on the right track and represent a new milestone in the project.”
Firstly, using molecular modelling techniques, the ICIQ team studies the proteins involved in the previous phase of the replication process. They design molecules that coordinate with the binding pockets of the proteins, suitable cavities for molecule binding, thus inhibiting replication in the early stages. These molecules are then prepared in ICIQ’s innovation laboratory.
Subsequently, the molecules synthesised in ICIQ’s laboratory are then analysed through DNA synthesis inhibition assays at IDIBGI. Based on the results obtained in these assays, the ICIQ team then goes back to the starting point to enhance the activity of the molecules and optimise their effectiveness. Dr. Félix Cuevas, ICIQ researcher and member of the BIST Community, is responsible for this part of the project.
The second approach is based on the synthesis of small peptides of around thirty amino acids, which mimic parts of the complex system of proteins involved in the early stages of DNA replication. The use of these peptides allows studying inhibition processes based on disrupting protein-protein interactions. Dr. Fernando Bravo, KTT Manager at ICIQ and member of the BIST Community, leads this approach alongside the computational chemistry group led by Prof. Feliu Maseras at ICIQ, which studies the fitting and molecular dynamics of these proteins over time. As Dr. Bravo explains, “disrupting the recognition process between proteins allows for the incorporation of innovative therapies that synergise with other treatments, ultimately resulting in more effective cancer therapies.”
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