Overview

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Two main research projects are currently active

1) Studies on the structure-activity of intracellular oligopeptidases - TOP (thimet oligopeptidase), PREP (or POP - prolyl oligopeptidase) and PREPL (prolyl oligopeptidase-like).

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The interaction with the active PREP accelerates the alpha-synuclein (α-Syn) polymerization-aggregation event. Despite the fact that α-Syn is not cleaved by PREP, factors that affect PREP conformation, including most of its inhibitors and an impairing mutation in its active site, influence the acceleration of α-Syn aggregation resulting from the interaction of these proteins. In such a way that PREP inhibitors are being considered potential drugs for synucleinopathies (e.g. Parkinson Disease). We are investigating this interaction by NMR and spectroscopic probes placed at specific sites of the PREP structure by the amber codon suppression technology. We are also investigating the α-Syn interaction with Prolyl endopeptidase-like (PREPL) protein, a structurally related protein to the serine peptidases belonging to the PREP family.

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2) Development of cyclic-peptide inhibitors for viral proteases (NS2B/NS3 proteases from Dengue Virus and Zika virus).

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The NS2B/NS3 protease process the viral poly-protein through cleavages at its cytosolic exposed portions. This activity is essential for the viral replication into the host cells. We are studying the proteases from Dengue and Zika viruses. We aim to develop inhibitors selected by a new method we constructed, witch consist of an in cell high-throughput screening coupled with a intracellular cyclic peptide library (based on the split intein mediated circular ligation of peptides and proteins - SICLOPPS - methodology) .