Atilio Reyes Romero
Prof. Alex Dömling, Dr. Matteo Gentili
Design, synthesis and in vitro screening of novel molecules to control the oligomeric state of malate dehydrogenase.
About the project:
The topic of this thesis is the design and the synthesis of compounds in order to interfere with the oligomerization of malate dehydrogenase of P. Falciparum (PfMDH). The crystal structure of PfMDH has recently been solved and the results are awaiting publication. The analysis of PfMDH structure revealed a tetrameric assembly, although isoforms of the enzyme from other species have been reported to be present as either dimers or tetramers. The oligomeric nature of PfMDH and the low degree of evolutionally conservation of the interface residues provide an opportunity for a highly specific protein interference approach. Further, our data shows that interference with aspartate metabolism in vivo results in a significant drop in parasitemia and strongly suggests that enzymes integral to aspartate metabolism are promising targets in the development of novel antimalarials.
Born in Isola della Scala (Verona), I graduated in Pharmacy Chemistry from the University of Parma with a thesis on organic synthesis of palmitoiletanolamide prodrugs for anti-inflammatory purposes. Furthermore I hold a postgraduate degree in drug design and development got at the University of Pavia and spent six months at the University of Innsbruck where I wrote a thesis in QSAR models in matched molecular pair analysis. I love modern art, especially Mirot, and I write haiku poetries as a hobby.
Helmholtz Zentrum München (6 months)
List of publications:
Synthesis and Enantiomeric Separation of a Novel Spiroketal Derivative: A Potent Human Telomerase Inhibitor with High in Vitro Anticancer Activity; Fuggetta MF, de Mico A, Cottarelli A, Morelli F, Zonfrillo M, Ulgher F, Peluso P, Mannu A, Deligia F, Marchetti M, Roviello G, Reyes Romero A, Dömling A and Spanu P; J. Med. Chem., 2016, 59 (19), pp 9140–9149,
Oligomeric interfaces as a tool in drug discovery: Specific interference with activity of malate dehydrogenase of Plasmodium falciparum in vitro; Lunev S, Butzloff S, Romero AR, Linzke M, Batista FA, Meissner KA, Müller IB, Adawy A, Wrenger C and Groves M; PLoS One, 2018; 13(4): e0195011. DOI: 10.1371/journal.pone.0195011
Oligomeric protein interference validates druggability of aspartate interconversion in Plasmodium falciparum; Batista FA, Bosch SS, Butzloff S, Lunev S, Meissner KA, Linzke M, Romero AR, Wang C, Müller IB, Dömling ASS, Groves MR, Wrenger C; MicrobiologyOpen, 2018; e779. Doi: 10.1002/mbo3.779
List of posters:
A New Toolkit in Drug Target Validation: the Protein Interference Assay; Reyes Romero A, HDDC 2018; April 26/27; Munich, Germany
How to Design Specific Molecules Interacting with Aspartate Aminotransferase of
P. Falciparum; Reyes Romero A, Groves MR and Dömling AS; EUROPIN Summer School on Drug Design, September 17 – 22, 2017; Vienna, Austria
List of presentations:
Atilio Reyes Romero
Department of Drug Design
School of Pharmacy
University of Groningen
Antonius Deusinglaan 1
9700 AD Groningen