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APPLICATIONS OF PEPTIDES NUCLEIC ACIDS (PNA) IN MOLECULAR MEDICINE AND BIOTECHNOLOGY
Minerva Biotecnologica 1999 September;11(3):175-85
Copyright © 1999 EDIZIONI MINERVA MEDICA
language: English
Conformational features of Peptidic Nucleic Acids for the rational design of biologically active PNAs and hybrid PNA-oligonucleotides
Saviano M., Bucci E., Romanelli A., Pedone C.
Centro di Studio di Biocristallografia del CNR and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, Dipartimento di Chimica, Napoli, Italy
The search for new oligonucleotides with improved properties represents an important step for the development of oligonucleotides as powerful biomolecular tools, antisense and antigene agents, molecular probes and biosensors. One of the most interesting of the new derivatives is Peptide Nucleic Acid (PNA), an analogue of DNA in which the backbone is a pseudopeptide rather than a sugar. PNA mimics the behaviour of DNA and binds complementary nucleic acid strands, with higher affinity and specificity than corresponding oligonucleotides. The unique properties of PNA open up novel molecular biology and biochemistry applications that are unachievable with traditional oligonucleotides and peptides. The non-charged nature of the PNA backbone is an important feature leading to higher thermal stability of PNA/DNA duplexes compared to DNA/DNA duplexes and stability of PNA duplexes with DNA independent of salt concentration. PNA oligomers are resistant to degradation by enzymes, and the lifetime of these compounds is extended both in vivo and in vitro. The direction of rational drug design of new PNA with specific functions depends critically on understanding the basic principles of specificity of biomolecular recognition for this class of molecules. Thus, the comparative analysis of conformational data on PNA/PNA, PNA/RNA, PNA/DNA duplexes and PNA2/DNA triplex represents the starting point for the design of new PNAs. In addition, the investigation of modified PNAs and PNA/DNA chimeras may provide a new generation of nucleic acid mimetics with large-scale application in biological systems.