Molecular Engineering of PNA Using Modified Uracil Derivatives and Porphyrins

PNAs (peptide nucleic acids) are among the most powerful tools in molecular biology and biotechnology, also for their versatility to be changed by chemical modifications. In the first part of thesis we describe the design and synthesis of uracil dimers, accurately designed to reinforce binding ability of uracil. Symmetric dimers were found to be biologically active, showing antiproliferative effect and erytroid differentiation inducing activities. Dissymmetric dimers were incorporated into PNA oligomers and tested toward complementary and mismatched DNA. In both case we found a cooperativity between the two uracil moieties In the second part we explored the use of porphyrins as spectroscopic sensor for structure assessment. Preliminary result showed a strong influence of porphyrins on PNA duplex conformation, giving rise to unexplored PNA conformations.