Tecnologie combinatoriali per l'identificazione di inibitori di enzimi ART : design, sintesi e screening di librerie pseudo-peptidiche

Combinatorial technologies for identifying enzymes ART inhibitors: design, synthesis and screening of pseudo-hexapeptidic libraries The subject of this thesis, peptides and peptidomimetics, recently has been an area of great interest for the drug discovery process. The work described in this thesis has been planned for and accomplished with combinatorial technologies. The aim has been to create new peptidomimetic libraries for the purpose of identifying synthetic molecules capable of mono-ADP-ribosyl-transferases. The work can be divided as follows: 1) The development of synthetic methodology for the production of a large number of compounds: synthesis of 480 pseudo- hexapeptides that contain an azabicyclo[X.Y.0] alkane amino acid residue. 2) Development of immunoassay for the screening of the peptidomimetic library and development of an affinity chromatography system to purify the intracellular ART enzyme. 3) Purification and quality control of the peptidomimetic library. The main result obtained from the work was the discovery of novel, selective pseudo-hexapeptides inhibitors of mono-ADP-ribosyl-transferases.