Research

The aims of the research developed in my laboratory can be summarized as follows:
➢ elucidation of the molecular mechanism of action of drugs interacting with nucleic acids, with established or potential therapeutic activity,
➢ molecular basis of receptor-ligand recognition,
➢ rational drug design and structure-activity relationship studies
➢ discovery of DNA/RNA aptamers able to bind and inhibit targets of pharmaceutical interest through combinatorial methods (SELEX).


The main research programs focus on the following two lines:
1. the design and study of the mechanism of action of known or novel drugs targeted at nucleic acids, alone or in complex with specific proteins, with potential applications in antitumor, antibacterial or antiviral chemotherapy: our aim is to design and investigate the mechanism of action of novel synthetic ligands targeted at specific sequences and/or structural contexts in DNA/RNA chains, in particular those relevant for therapeutic treatment (TAR-RNA, cTAR, PBS, PPT of the HIV genome, quadruplex DNA of the human telomeric sequence or of oncogenes). We characterize the physico-chemical parameters of DNA/RNA recognition of established or potential drugs and elucidate the mechanism of action of the new compounds in terms of recognition of specific nucleic acid sequences and interference with the activity of essential helix-tracking enzymes.

2. the development of nucleic acids aptamers as biosensors employing the technique known as SELEX, or Systematic Evolution of Ligands by Exponential enrichment, a methodology evolved from the unique insight that nucleic acids have sufficient capacity for forming a variety of two- and three-dimensional structures and sufficient chemical versatility available within their monomers to act as ligands with virtually any compound. This powerful technique allows the screening of large combinatorial library of nucleic acids with particular recognition properties.


Staff Expertise

My main expertise concerns the evaluation of the affinity between small molecule compounds and nucleic acids of viral and oncological interest. My main research interest is the study of the interaction of small molecule drugs with nucleic acids alone and in the context of protein complexes, namely:

1. The evaluation of the binding of the small molecule to nucleic acids, such as:
a. The characterization of the physico-chemical properties of the chosen molecules in acqueous solution, in order to evaluate the best conditions for spectroscopic and electrophoretic assays.
b. The evaluation of the affinity of the compounds for the nuclei acids outlined above to determine binding affinity and selectivity by spectroscopic, electrophoretic and microcalorimetric methods

2. The evaluation of the effect(s) of the compounds on the complex formed by the nucleic acids and their protein targets.
a. Evaluation of the inhibition properties of selected compounds on complex formation between nucleic acids and proteins is performed by spectroscopic, electrophoretic and microcalorimetric methods

3. the development of microarrays based on aptamers as biosensors.
a. The development of aptamers as array nanosensors for simultaneous multianalyte analysis is in collaboration with Veneto Nanotech.

Key words
Drug design. Antitumor drugs. Antiviral drugs. HIV-1 Nucleocapsid. TAR RNA. Quinolones. Topoisomerases. Nucleic acids. Aptamers.

Students interested in carrying out their experimental thesis in the laboratory of Prof.ssa Gatto are kindly asked write an to e-mail, attaching their CV and a motivation letter explaining the reasons for the request.