Sintesi di nuovi monomeri e oligomeri di acidi peptido nucleici con applicazioni in diagnostica e come potenziali nuovi agenti terapeutici

Synthesis of new monomers and oligomers of modified peptide nucleic acids with diagnostic and potentially therapeutic applications Peptide nucleic acids (PNA) are DNA mimics in which the sugar phosphate unit is replaced by a pseudo-peptide chain of N-(2-aminoethylglycine) units, each bearing a nucleobase. PNA binds complementary DNA and RNA with high sequence specifity and therefore has potential application as an anti-sense and anti-gene agent, and in genetic diagnostics. In this Ph.D. thesis is described the synthesis of a new class of modified PNA monomers, called hydrazinoPNA (hydPNA), and the study for setting up the appropriate coupling conditions for the dimerization in view of their oligomerization. In these monomers the primary terminal amino group of the aminoethylglycine unit of aegPNA is replaced with a hydrazine moiety. An appropriate choice of two orthogonal protecting groups on the two hydrazine nitrogen atoms makes it possible to drive their coupling with other monomers selectively on one or the other nitrogen atom, thus obtaining two different types of PNA dimers. In this work is also described the synthesis and the preliminary study about the oligomerization of another modified PNA monomers class, called azaPNA, in which the methylene group of the glycine is replaced by an NH group. Metal conjugated PNA monomers and oligomers synthesis and electrochemical studies are also reported. Functionalization of PNA monomers and oligomers with the phtalimido group as elecrochemical probe is also presented such as their electrochemical activity.