Biotechnological drugs

The use of peptides to prevent binding between CD47 and SIRPα proteins in order to avoid infections – Paula Quesada Martínez

7 May, 2022 por Anabel Torrente Leave a Comment

CD47 is a protein found on the surface of the cells of infectious agents, such as viruses and bacteria. Its interaction with the signal-regulatory protein alpha (SIRPα) of the cells in our immune system induces an antiphagocytic signal, thus preventing phagocytosis, the process by which the cells in our immune system trap infectious agents and eliminate them.
Certain tumours use this mechanism to escape the action of the immune system. The same mechanism is also used by pathogens, such as the SARS-CoV-2 coronavirus or Mycobacterium tuberculosis, which induce excessive expression of CD47 to overcome our body’s defence barriers easily. Since the activation of CD47 expression is not related to the specific interaction of the pathogen with our cells, it could be used as a therapeutic target for dealing with a wide variety of infectious agents. In fact, the use of compounds with anti-CD47 activity during viral infection has been shown to promote immunity and help clear the virus more quickly.
The main objective of this work is to discover new peptides (small proteins with less than 50 amino acids), which are resistant to the enzymes that break them down (proteases) and have high affinity for either CD47 or SIRPα, so as to inhibit the interaction between them.
The activity of these peptides will then be evaluated through what is known as affinity assays. The aim of these assays is to measure the degree of affinity of the peptides with these proteins and find out more about how they bind and interact with them.

Keywords: CD47; SIRPα; peptides; infections

Directed by: Macarena Sánchez Navarro

Application of new methods for analyzing the safety of biopharmaceuticals – Mario Martínez Popeti

7 May, 2022 por Anabel Torrente Leave a Comment

Biopharmaceuticals are pharmaceutical products manufactured from biological sources, such as cell cultures, animals, etc. Examples of biopharmaceuticals include vaccines and therapeutic proteins, among others. In this research, we present a study to evaluate the safety of romiplostim, the active ingredient of drug, used to increase the level of platelets in blood. Romiplostim is a protein and as such, is susceptible to changes in its structure. These changes can be caused, for example, by exposure to high temperatures or poor storage. This can inhibit the function of the drug or even produce undesirable reactions in the patient.
In this research, we analyze these structural modifications using a multi-attribute method, involving digestion of the romiplostim (cleavage of its structure into peptides), separation of the resulting peptides and detection by mass spectrometry. The drug is subjected to certain specific situations in the laboratory that might induce changes in its structure (for example, exposure to light). In this way, we evaluate the stability of its properties when subject to a range of different conditions, in order to assess and ensure its safe use.

Keywords: biopharmaceuticals; therapeutic proteins; romiplostim; multi-attribute method; safety

Directed by: Natalia Navas Iglesias

Quantitative stability analysis of nivolumab, an anti-tumour drug – Lorena Jiménez Morán

7 May, 2022 por Anabel Torrente Leave a Comment

Cancer, which involves an uncontrolled increase in cell proliferation and growth, remains one of the leading causes of death worldwide. Our immune system tries to eliminate this excess proliferation of cells from the body. However, cancer has mechanisms that help it evade the actions of the immune system, making it very difficult to fight effectively.
New therapies and drugs are being developed to combat this disease. One such drug is nivolumab, which is used to treat lung cancer, among others. However, it has an important disadvantage in terms of its high price and its loss of efficacy in certain storage conditions or during hospital use, because of its protein nature. In this project a quantitative technique (MicroScale thermophoresis) is used to analyze the efficacy and stability of nivolumab over time and when subjected to conditions similar to those applicable during handling of the drug in hospitals.

Keywords: cancer; nivolumab; efficacy; stability; MicroScale thermophoresis

Directed by: Jesús Hermosilla Fernández

Combatting bacteria with very small molecules of silver-DNA – Carmen López Chamorro

7 May, 2022 por Anabel Torrente Leave a Comment

One of the greatest challenges in pharmaceuticals research today is the increase in antibiotic resistance, i.e. the ability of microorganisms to survive in the presence of antibiotics.
This Master’s thesis focuses on developing new drugs with innovative mechanisms using AgI (silver) ions, which can potentially prevent the growth of bacteria (antibacterial activity) and fungi (antifungal activity). DNA molecules (with a double-stranded structure) are used to transport these ions thanks to their high selectivity and versatility in terms of size, shape and sequence. To do this, chemical molecules (nucleobases) that are part of DNA (called guanine and adenine) are replaced by similar molecules (7-deazaguanine and 7-deazaadenine). These deaza-DNA molecules can transport the AgI ions inside the double-stranded DNA. In this way, customized deaza-DNA structures can be formed with base pairs mediated by AgI that can be studied by cell assays. Using this method, we can endow DNA molecules with new antibacterial properties present in the AgI without modifying their geometry. This provides a new way of studying drugs that can help avoid antibacterial resistance.

Keywords: DNA; deaza-DNA; AgI ions; nanostructures.

Directed by: Miguel Ángel Galindo Cuesta

Do the Moderna and Pfizer vaccines remain stable after handling during administration? – Airan Braulio Alonso García

7 May, 2022 por Anabel Torrente Leave a Comment

The pandemic has brought about a revolution in the field of research, especially in pharmacology. Research studies aimed at finding an effective solution against COVID-19 have increased exponentially since the start of the pandemic. Various vaccines are now on sale and have themselves become the subject of numerous research studies. These studies seek to monitor the safety, efficacy, stability, and other aspects of these drugs.

This research studies the stability of the Moderna and Pfizer vaccines during distribution and handling in hospital settings to assess whether they maintain their physicochemical properties. To this end, various different stress tests are carried out on the vaccines in the laboratory. These are similar to the stresses to which the vaccines may be exposed during distribution and handling. They are also subjected to more violent stress tests, such as shaking, high temperatures, and exposure to natural or artificial light, among others so as to verify that the particulate that makes up the vaccine remains stable. The aim of this research is to find out whether we can reduce the strict measures that must be followed when distributing the vaccines and administering them to the population.

Keywords: stability; physicochemical properties; vaccines; COVID-19

Directed by: Natalia África Navas Iglesias