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Rivista di Biologia Molecolare e Biotecnologie
Indexed/Abstracted in: EMBASE, Science Citation Index Expanded (SciSearch), Scopus
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New trends in chemistry and biotechnology of peptide nucleic acidS
Minerva Biotecnologica 2008 December;20(4):139-47
Peptide nucleic acids (PNAs) and modified PNAs for DNA targeting
Corradini R., Sforza S., Tedeschi T., Calabretta A., Accetta A., Tonelli A., Marchelli R.
Department of Organic and Industrial Chemistry University of Parma, Parma, Italy
In this paper we describe the recent advances in the synthesis and application of polyamide DNA analogues peptide nucleic acid (PNAs) and modified PNAs, obtained by our research group in the context of national and international projects dedicated to DNA targeting in the fields of diagnostics and drug development. Modification of the PNA backbone by inserting substituents which create stereocenters either at position C2, C5 or both have been studied. Racemization-free synthetic procedures were developed in order to preserve the optical purity of the modified chiral PNAs. The control of stereochemistry allowed a fine-tuning of the DNA binding properties in accordance with the preference of each PNA for right- or left-handedness. Modified nucleobases are also shown to be very promising for increasing DNA binding, allowing additional specific interactions with the target base. The availability of modified PNAs has provided new efficient tools for the recognition of DNA sequences with single nucleotide polymorphism (SNP), which have been applied to the detection of DNA relevant to medical diagnosis as well as to food analysis. PNA probes to identify genetically modified organisms (GMOs), allergens, and plant varieties have been developed and used in combination with several analytical techniques. Ultrasensitive detection of DNA was also achieved using PNA probes in a microfluidic platform. Moreover, PNAs and modified PNAs have been used in therapeutics and were shown to inhibit gene expression by an anti-gene mechanism, a promising strategy for the development of new, highly specific antitumor drugs.