Protein crystallography, structure-based drug design, antibody engineering
Our laboratory carries out structural studies on various proteins of biological or medicinal interest using protein crystallography. Among our targets, protease from HIV, antibody fragments as well as other human enzymes take a prominent position.
Human carbonic anhydrases (CA) play important roles in various physiological and pathological processes (e.g. tumorigenicity, obesity, and epilepsy) and thus many CA isoenzymes represent established diagnostic and therapeutic targets. In particular, we have a significant interest in the development of selective inhibitors targeting carbonic anhydrase isoform IX (CAIX), a tumour-associated transmembrane isoenzyme, the overexpression of which is induced by hypoxia. CA IX is used as a tumour marker and as a prognostic factor for several human cancers and thus represents a valuable target for antitumor therapy.
Monophosphate 5′-nucleotidases are ubiquitous enzymes that catalyze the dephosphorylation of nucleoside monophosphates and thus help regulate cellular pools of nucleotides. In addition to their physiological role, the human orthologues of these enzymes also participate in activation of nucleoside analogues used as antiviral and anticancer agents. Monophosphate 5′-nucleotidases are thus considered targets for development of inhibitors to increase the efficacy of clinically used nucleoside analogues.
In addition to structural projects, several recombinant antibody fragments of potential diagnostic and/or immunotherapeutic use (e.g. against human carbonic anhydrase IX, CD44, and CD3) have been prepared and characterized in our laboratory with the aim to improve their radionuclide labelling or to introduce further useful properties.
Link to Protein data bank (PDB) deposits: www.rcsb.org.
Last change: September 25, 2017