Design, synthesis and development of peptide nucleic acid (PNA) based analogues for miRNAs targeting in therapeutic and diagnostic fields
PNAs are nucleic acid analogues which have implemented affinity, specificity and are resistant to enzymatic degradation. All these features make PNA an outstanding candidate as antisense, antigene, miRNA targeting molecules as well as capture probe in diagnostic applications.
Peptide nucleic acid (PNA) is an attractive and powerful nucleic acid mimic developed by Nielsen in 1991. Recently, miRNAs, are class of non-coding RNAs which have emerged as novel cellular regulators and a biomarkers; being deregulated in various human diseases. miRNAs represent an appealing class of molecules in both drug development and diagnostic field. The first research activity regards the design and synthesis PNAs as analogues of miRNA-34a which performs as tumour suppressive in Neuroblastoma. The PNA-based analogues were synthesized, and their interaction with two binding sites on the target MYCN mRNA was investigated by molecular dynamics simulation and spectroscopic techniques (UV, CD, NMR). The second research activity is based on PNAs as smart receptor probes for multiple detection of miRNAs biomarker. PNA based smart probes (fluorescent and electrochemical) were synthesized and characterized by spectroscopic/electrochemical techniques. These smart probes were developed to address the lack of fast /cost effective diagnosis in pancreatic cancer and coeliac disease. The third research activity is based on the design of new chiral analogues of PNA, these analogues will be used for the oligomers synthesis to establish the binding properties with natural nucleic acids.
– Moccia M, Mercurio F.A., Langella, Piacenti V., Leone M., Adamo MFA, Saviano M. Structural insight on tiny peptide nucleic acid (PNA) analogues of miRNA-34a: an in silico and experimental integrated approach. Frontiers in chemistry, 2020, 1128.
– Piacenti V., Langella, E., Autiero I., Nolan J.C., Piskareva O., Adamo M.F.A, Saviano M., Moccia M. A combined experimental and computational study on peptide nucleic acid (PNA) analogues of tumor suppressive miRNA-34a. Bioorganic Chemistry; 2019, Vol. 91, 103165.
– M. Moccia, Caratelli V., Cinti S., Pede B., Avitabile C., Saviano M., A. L: Imbriani, Moscone D., Arduini F., Biosensors and Bioelectronics, 2020, vol 165, 112371.
– Moccia M., Antonacci A., Saviano M., Caratelli V., Arduini F., Scognamiglio V. Trends in Analytical Chemistry, 2020 132, 116062.