Atilio Reyes Romero




University of Groningen


Prof. Alex Dömling, Dr. Matteo Gentili

Research Topic:

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.


Personal information:

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), Giotto Biotech (3 months)


List of publications:

The (R)-Enantiomer of the 6-Chromanol Derivate SUL-121 Improves Renal Graft Perfusion via Antagonism of the Α1-Adrenoceptor. Nakladal D, Buikema H, Romero AR, Lambooy SPH, Bouma J, Krenning G, Vogelaar P, van der Graaf AC, Groves MR, Kyselovic J et al.; Sci. Rep. 2019, 9 (1), 13; DOI:10.1038/s41598-018-36788-0

Production of “Biobetter” Variants of Glucarpidase with Enhanced Enzyme Activity. Al-Qahtani AD, Bashraheel SS, Rashidi FB, O’Connor CD, Romero AR, Domling A, Goda SK; Biomed. Pharmacother. 2019, 112, 108725; DOI:10.1016/j.biopha.2019.108725

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 et al.; Microbiology Open 2019, e779; DOI:10.1002/mbo3.779

Rapid Approach to Complex Boronic Acids. Neochoritis CG, Shaabani S, Ahmadianmoghaddam M, Zarganes-Tzitzikas T, Gao L, Novotná M, Mitríková T, Romero AR, Irianti MI, Xu R et al.; Sci. Adv. 2019, 5 (7), eaaw4607; DOI:10.1126/sciadv.aaw4607

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

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,
DOI: 10.1021/acs.jmedchem.6b01046


List of posters:

Allosteric Inhibition in Vitro of Plasmodium Falciparum Malate Dehydrogenase by Small Molecule and its Proposed Mechanism of Action.Romero AR , Popowicz G, Groves M, Sattler M, Dömling A; New Frontiers in Structure-Based Drug Discovery; Sep23 - 25, 2019, Florence, Italy

Fragment Based Design to Disrupt the Oligomeric Interface of Plasmodium Falciparum Malate Dehydrogenase.Romero AR, Lunev S, Popowicz P, Calderone V, Gentili M, Plewka J, Kozak M, Sattler M, Dömling ASS and Groves MR; Helmholtz Training Course on Integrative Structural Biology, Oct 22-26, 2018 at CSSB, Hamburg, Germany

A New Toolkit in Drug Target Validation: the Protein Interference Assay;Romero AR, Batista FA, Bosch S, Lunev S, Linzke M, Groves M and Wrenger C; 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: