| Abstract |
The project focuses on DNA and RNA oligonucleotides with conformationally constrained internucleotide linkages which result either from stereoisomery or from sterically partially restricted rotation around single bond. Various types of constrained linkages give rise to entropically more advantageous pre-organized conformations of sugar-phosphate backbone in DNA and RNA oligonucleotides, which may radically influence both mutual oligonucleotide interactions and the interactions with proteins. Study of properties of specifically modified backbones by advanced physico-chemical and theoretical methods would enable to clarify, on molecular level, the behavior of such modified entities in relevant biological experiments. Project´s asset is seen in elaboration of new synthetic strategies in chemistry of phosphonic acids and in gaining knowledge on the relationship between structure and properties of the modified internucleotide backbones. Besides, utilization of DNA and RNA oligonucleotides with pre-organized structure is envisaged in diagnostics and especially as possible candidates for gene therapy. |
