Institute of Crystallography - CNR

Design and synthesis of oligonucleotides for diagnostic and therapeutic use

The research is mainly focused on the design and synthesis of nucleic acid derivatives, both for the realization of oligonucleotide biomimetic models, in vivo and in vitro studies, and for the synthesis of new antiviral drugs analogous to nucleosides.

Synthetic oligonucleotides are extremely versatile biopolymers that are used in a wide range of applications from biological, biomedical and nanotechnology research to therapeutic and diagnostic fields. By automated synthesis using the phosphoramidite method with commercial or appropriately synthesized phosphoramidites, we have developed new oligonucleotide derivatives with tailored properties for this research area of interest.

ODN sequences, modified or not, represent biomimetic models for studies on oxidative DNA damage, enzymatic repair system and identification of purine lesions (8-oxo-purine and 5′,8-cyclopurine). Thanks to a sophisticated analytical protocol, these lesions have been detected in genomic and mitochondrial DNA: of neurodegenerative cell models; in tissue biopsies of patients with Crohn’s disease, ulcerative colitis and severe obesity, they highlight the link between oxidative stress and inflammatory diseases. This multidisciplinary approach aims to identify potential new biomarkers associated with these diseases.
The objective of the research is also the study of the interaction of ODNs models (G-quadruplex, TFOs, etc.) with pharmacologically active molecules, proteins and metal ions, which find application both as therapeutic agents and in the realization of biocompatible chiral probes (such as Carbon based nanoparticles/ODNs).
The development of new antiviral drugs, analogues of nucleosides, is also a topic of study.

Reference works

– Increased Levels of 5′,8-Cyclopurine DNA Lesions in Inflammatory Bowel Diseases. Masi, A.; Fortini, P.; Krokidis, M.G.; Romeo, E.F.; Bascietto, C.; De Angelis, P.; Guglielmi, V.; Chatgilialoglu, C. Redox Biol. 2020, 34, 101562.
– Oxygen Dependent Purine Lesions in Double-Stranded Oligodeoxynucleotides: Kinetic and Computational Studies Highlight the Mechanism for 5′,8-Cyclopurine Formation. Chatgilialoglu, C.; Eriksson, L.A.; Krokidis, M.G.; Masi, A.; Wang, S; Zhang, R. J. Am. Chem. Soc. 2020, 142, 5825–5833.
– Diastereomeric Recognition of 5′,8-cyclo-2′-Deoxyadenosine Lesions by Human Poly(ADP-ribose) Polymerase 1 in a Biomimetic Model. Masi, A.; Sabbia, A.; Ferreri, C.; Manoli, F.; Lai, Y.; Laverde, E.; Liu, Y.; Krokidis, M.G.; Chatgilialoglu, C.; Faraone Mennella, M.R. Cells 2019, 8, 116.
– Pyrazinoporphyrazines with Externally Appended Pyridine Rings. 13. Structure, UV-Visible Spectral Features, and Noncovalent Interaction with DNA of a Positively Charged Binuclear (Zn-II/Pt-II) Macrocycle with Multimodal Anticancer Potentialities. I. Manet, F. Manoli, M.P. Donzello, E. Viola, A. Masi, G. Andreano, G. Ricciardi, A. Rosa, L. Cellai, C. Ercolani, and S. Monti. Inorganic Chemistry 2013, 52, 321-328.

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