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The University of Southampton
OLIGOMED - Oligonucleotides for medical applications

ESR Project. 6, Research Institutes of Sweden (SE)

Enhancing ASO action and mRNA regulation in cardiometabolic disease

ESR6 Mónica Andreia Monteiro Lopes
Mónica Andreia Monteiro Lopes

Mónica Monteiro Lopes received her bachelor’s degree in Applied Chemistry from NOVA University of Lisbon, and her master’s degree in Bioorganic Chemistry from the same institution.

During her bachelor’s final year, she worked in Sundaresan Prabhakar’s laboratory from the LAQV@REQUIMTE network, under the supervision of Prof. Paula Branco. The project aimed to derivatize β-cyclodextrin with organic chromophores based on coumarin. More specifically, she synthesized, purified, and characterized coumarin-based compounds and cyclodextrins for binding through click chemistry.

Mónica kept working under the supervision of Prof. Paula Branco, on her master’s thesis. The primary goal was to develop a pathway for synthesizing the Cernumidine alkaloid and potential analogues. She conducted multi steps’ synthesis, monitored reactions, purified compounds, and characterized them using ATR-FTIR, 1D NMR, and GC-MS techniques. Her contributions to this work resulted in the research paper “Synthetic Approaches to a Challenging and Unusual Structure an Amino Pyrrolidine Guanine Core” published by Molecules journal.

After completing her studies, she began working as Research Fellow at CENIMAT|i3N within the GREEN PILS 4 CO2 project, overseen by Dr. Marta Corvo and Dr. Marcileia Zanatta. Mónica synthesized polymeric ionic liquids, formulated biocomposites, characterised them, and investigated their ability to capture CO2 using NMR spectroscopy (1D and 2D NMR spectra, obtained via liquid state, solid-state, HR-MAS, and High-Pressure NMR, and MRI). Some of her results have been published in the scientific article “Handling CO2 sorption Mechanism in PIL@IL Composites” in the Journal of CO2 Utilization and in the book chapter “Molecular Interactions in Ionic Liquids: The NMR Contribution toward Tailored Solvents” by IntechOpen.

Besides work, Mónica won a grant from Real Sociedad Espanhola de Química to attend the  XIII Manuel Rico NMR Summer School at the University of Zaragoza, where she was able to revise and, especially to learn more about the NMR technique.

 

   
Host institution Research Institutes of Sweden, Department Chemical Process and Pharmaceutical Development, Södertälje, Sweden
   
Supervisor Dr. Ulf Tedebark
   
Co-Supervisors   Dr. Martin Bollmark, RISE (industrial)
Prof. Eugen Stulz, University of Southampton, UK (academic)
Prof. Roger Strömberg, Karolinska Institutet, Sweden (academic)

 

Project description

The aim of this ESR PhD project will be: [1] methodology development of click conjugation techniques to allow construct formation including at least one oligonucleotide derivative, and at least two other derivatives, e.g. mAb, peptide, protein, aptamer, carbohydrate, lipid, small molecule. [2] Methodology development to allow manufacturing of constructs using continuous flow technology, e.g. solid-phase synthesis of chemical entities for later on-resin construct formation, immobilised enzyme catalysts for highly selective manipulation. [3] Process development and optimization for manufacturing of constructs aimed for pre-clinical and clinical trial evaluations based on consortium needs.

 

Secondments

This project is carried out in strong collaboration with the following groups:

Host laboratory

Research activities in the group of Tedebark and Bollmark are focused on orthogonal conjugation techniques to obtain constructs containing combination of oligonucleotide derivatives and at least one other entity from the groups of peptides, proteins (mAb), carbohydrates, lipids or small molecules to allow targeted delivery and tailored release conditions at the site of action. This involves organic chemistry transformation and introduction of handles for selective conjugation as well as preparation of larger amounts of building blocks. The laboratory (being the former Process Development and Pharmaceutical Department of AstraZeneca) has full access to equipment to facilitate process development of larger scale synthesis of building blocks and automated synthesis instruments for subsequent introduction into oligomers.

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