Innovative results in the Biostructure Section have been achieved during the year 2003 in the field of modified oligonucleotides. The PNAs are DNA analogues in which the sugar-phosphate backbone has been substituted by an aminoethylglycine; thanks to their ability to tightly bind complementary DNA and RNA and to their high resistance to enzymes they have been widely used as antisense and antigene molecules. It has been demonstrated that PNA do not bind transcription factors because of their conformation and lack of charge. Conjugation of PNA to DNA results in very soluble molecules, often reported as chimeras, able to bind to proteins such as transcription factors and therefore useful as decoy molecules.
Competition experiments of oligonucleotides (ODNs) and chimeras on transcription factors (TF) such as NF-kB and Sp1 demonstrated that PNA-DNA-PNA conjugates compete with natural ODNs in the protein binding and are also able to displace an ODN from the ODN-TF complex. The results obtained so far show the high potential of PNA-DNA conjugate in therapies aimed at the control of gene expression.
Innovative results in the Bioimaging Section n have been achieved in the Coronary artery disease (CAD), a myocardial disorder with a great social impact. The aim to use radionuclide imaging in CAD patients is twofold. The early diagnostic identification of myocardial ischemia, by radionuclide techniques, in patients with higher risk of CAD. As well as, the evaluation of diagnostic criteria to submit patient with known CAD to medical or surgical treatment (revascularization procedures) and the assessment of the beneficial effects of such treatment.
Our Bioimaging Section is currently investigating the value of myocardial ischemia, assessed by radionuclide techniques, in predicting cardiac events (i.e. myocardial infarction and cardiac death) in patients with suspected or known CAD. Our next studies may be useful to best understand when patients submitted to revascularization procedures have to be submitted to evaluation of myocardial ischenia during the follow-up, to prevent cardiac event.
In the Catania Section the research activity has been mainly focused in the protein's misfolding and aggregation studies. Particular attention has been paid to the elucidation of the role played by some transition metals, particularly copper and zinc, in protein fibrillogenesis which is often involved in the etiopathogenesis of several neurodegenerative diseases including prion and Alzheimer's diseases or represents a clinical marker in chronic syndromes like type II diabetes. The studies were essentially tackled by a chemical point of view and were addressed to the understanding of the molecular mechanisms involved in the structural and conformational modifications, subsequent to metal ion interaction, of oligopeptides relevant to structural or functional domains of the proteins implicated in the above cited pathologies.
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