Adelyn María Betances Mora

Biography

I began my studies in 2018 at the Pontifical Catholic University Mother and Teacher (PUCMM), Santiago Campus, Dominican Republic, where I graduated with a Bachelor’s degree in Chemistry in 2022. I then received a scholarship from the Ministry of Higher Education, Science, and Technology (Mescyt) of the Dominican Republic to pursue a Master’s degree in Advanced Studies in Chemistry at the University of Seville. I specialized in the structural determination of chemical substances and molecular chemistry, covering aspects from synthesis to applications. In my Master’s thesis, I used advanced NMR techniques (specifically saturation transfer difference STD-NMR spectroscopy) to investigate the interactions between glycomimetics and proteins.

Research project objectives

In this DC position, my research will focus on the application of advanced NMR techniques to validate and characterize molecular interactions involving enzymes related to cancer. I will start with NMR validation of identified hits and provide detailed pharmacophore information of these validated hits using multifrequency NMR spectroscopic approaches like DEEP-STD NMR fingerprinting approaches. I will further elucidate structural details of enzyme-inhibitor and scFv-combotope complexes employing also novel multisolvent-STD NMR techniques. Additionally, I will explore “on-cell” double-difference STD NMR techniques on scFv-loaded engineered NK cells. My training will include structural biology, advanced NMR techniques, state-of-the-art high-throughput screening (HTS), and NK cell engineering.

Chemical Science at the University of Seville (University of Seville) Consejo Superior de Investigaciones Científicas (CSIC)/ Instituto de Investigaciones Químicas (IIQ).

The host department and laboratories fully meet the requirements for the successful execution of the research project. Access to the facilities at the Chemical Research Institute (IIQ) will be available.
IIQ: The laboratories are well equipped with a full range of spectroscopic (5xNMR instruments, UV-Vis, FT-IR, 2xMS, Maldi-TOF), X-ray diffraction and analytical techniques.

Selected papers:

1.Rocha, G.; Ramírez-Cárdenas, J.; Padilla-Pérez, M. C.; Walpole, S.; Nepravishta, R.; García-Moreno, M. I.; Sánchez-Fernández, E. M.; Ortiz Mellet, C.; Angulo, J.; Muñoz-García, J. C. Speeding-up the Determination of Protein–Ligand Affinities by STD NMR: The Reduced Data Set STD NMR Approach (Rd-STD NMR). Anal. Chem. 2024. https://doi.org/10.1021/acs.analchem.3c03980.

2.Silva-Díaz, A.; Ramírez-Cárdenas, J.; Muñoz-García, J. C.; de la Fuente, M. C.; Thépaut, M.; Fieschi, F.; Ramos-Soriano, J.; Angulo, J.; Rojo, J. Fluorinated Man9 as a High Mannose Mimetic to Unravel Its Recognition by DC-SIGN Using NMR. J. Am. Chem. Soc. 2023, 145 (48), 26009–26015. https://doi.org/10.1021/jacs.3c06204.

3.Nepravishta, R.; Ramírez-Cárdenas, J.; Rocha, G.; Walpole, S.; Hicks, T.; Muñoz-García, J. C.; Angulo, J. Fast Validation of Static and Dynamic 3D Models of Weak Protein Ligand Complexes from STD NMR Spectroscopy. ChemRxiv 2023. https://doi.org/10.26434/chemrxiv-2022-b7s0x-v2.

4.Monaco, S.; Angulo, J.; Wallace, M. Imaging Saturation Transfer Difference (STD) NMR: Affinity and Specificity of Protein–Ligand Interactions from a Single NMR Sample. J. Am. Chem. Soc. 2023, 145 (30), 16391–16397. https://doi.org/10.1021/jacs.3c02218.

5.Gabrielli, V.; Kuraite, A.; da Silva, M. A.; Edler, K. J.; Angulo, J.; Nepravishta, R.; Muñoz–García, J. C.; Khimyak, Y. Z. Spin Diffusion Transfer Difference (SDTD) NMR: An Advanced Method for the Characterisation of Water Structuration within Particle Networks. J. Colloid Interface Sci. 2021, 594, 217–227. https://doi.org/https://doi.org/10.1016/j.jcis.2021.02.094.

6.Gabrielli, V.; Muñoz-García, J. C.; Pergolizzi, G.; de Andrade, P.; Khimyak, Y. Z.; Field, R. A.; Angulo, J. Molecular Recognition of Natural and Non-Natural Substrates by Cellodextrin Phosphorylase from Ruminiclostridium Thermocellum Investigated by NMR Spectroscopy. Chem. – A Eur. J. 2021, 27 (63), 15688–15698. https://doi.org/https://doi.org/10.1002/chem.202102039.

7.Park, J. B.; Kim, Y. H.; Yoo, Y.; Kim, J.; Jun, S.-H.; Cho, J. W.; El Qaidi, S.; Walpole, S.; Monaco, S.; García-García, A. A.; et al. Structural Basis for Arginine Glycosylation of Host Substrates by Bacterial Effector Proteins. Nat. Commun. 2018, 9 (1), 4283. https://doi.org/10.1038/s41467-018-06680-6.

8.Sequeira, S.; Kavanaugh, D.; MacKenzie, D. A.; Šuligoj, T.; Walpole, S.; Leclaire, C.; Gunning, A. P.; Latousakis, D.; Willats, W. G. T.; Angulo, J.; et al. Structural Basis for the Role of Serine-Rich Repeat Proteins from Lactobacillus Reuteri in Gut Microbe–Host Interactions. Proc. Natl. Acad. Sci. 2018, 115 (12), E2706–E2715. https://doi.org/10.1073/pnas.1715016115.

9.Monaco, S.; Tailford, L. E.; Juge, N.; Angulo, J. Differential Epitope Mapping by STD NMR Spectroscopy To Reveal the Nature of  Protein-Ligand Contacts. Angew. Chem. Int. Ed. Engl. 2017, 56 (48), 15289–15293. https://doi.org/10.1002/anie.201707682.

10.Muñoz-García, J. C.; Chabrol, E.; Vivès, R. R.; Thomas, A.; de Paz, J. L.; Rojo, J.; Imberty, A.; Fieschi, F.; Nieto, P. M.; Angulo, J. Langerin–Heparin Interaction: Two Binding Sites for Small and Large Ligands As Revealed by a Combination of NMR Spectroscopy and Cross-Linking Mapping Experiments. J. Am. Chem. Soc. 2015, 137 (12), 4100–4110. https://doi.org/10.1021/ja511529x.

11.Gong Y, Klein Wolterink RGJ, Gulaia V, Cloosen S, Ehlers FAI, Wieten L, Graus YF, Bos GMJ, Germeraad WTV. Defucosylation of tumor-specific humanized anti-MUC1 monoclonal antibody enhances NK cell-mediated anti-tumor cell Cytotoxicity. Cancers, May 2021, 13, 2579.

12.Gong Y, Klein Wolterink RJG, Wang JX, Bos GMJ, Germeraad WTV. Generation chimeric antigen receptor Natural Killer cells for tumor immunotherapy. J Hematol Oncol. 2021. 14:73.

13.Huijskens MJAJ, Walczak M, Sarkar S, Atrafi F, Senden-Gijsbers BLMG, Bos GMJ, Wieten L, Germeraad WTV. Ascorbic acid promotes proliferation of NK cell populations in culture systems applicable for NK cell therapy. Cytotherapy. 2015 May;17(5):613-20.

14.Sarkar S, Germeraad WTV, Rouschop KM, Steeghs EM, van Gelder M, Bos GMJ, Wieten L. Hypoxia induced impairment of NK cell cytotoxicity against multiple myeloma can be overcome by IL-2 activation of the NK cells. PLoS One. 2013 May 28;8(5):e64835.

15.Cloosen S, Arnold J, Thio M, Bos GMJ, Kyewski B, and Germeraad WTV. Expression of tumor-associated differentiation antigens CEA and MUC1 glycoforms in human thymic epithelial cells: 2implications for self-tolerance and tumor therapy. Cancer Res. 67(8): 3919-3926, 2007.