Physiological activities of synthetic analogs of polynucleotides

Abstract

The term polynucleotide is usually used for an analog or a fragment of nucleic acids. As with other important natural compounds, more distant analogs of polynucleotides, were synthesized and studied. In this review polymers which have backbones analogous to those of plastics and substituents analogous to those of polynucleotides are described; further in the text these compounds are named polynucleotide analogs. The interactions of polynucleotide analogs with natural polynucleotides and related proteins are described. These interactions strongly depend on the electric charge of polynucleotide analogs. Electroneutral analogs of polynucleotides interact with natural polynucleotides in a specific manner forming base-pair type complexes. On the other hand, the enzymes of nucleic acid synthesis are not directly bound by these polymers. Because neither polynucleotide analogs nor complexes of these analogs and natural polynucleotides can act as templates in biosynthesis, polynucleotide analogs can be used to block the natural ones and thus, to act as template-specific inhibitors of nucleic acid and protein biosynthesis. This inhibitory action of polynucleotide analogs is strong and specific in cell-free systems, and because they are not biodegradable it may be assumed that the effects of these polymers on cells or animals would also be strong and long-lasting. However, this is not the case; these effects were found to be rather weak and short-lasting. The observed decrease in effectiveness is the result of two factors: a) the ability of polymers to penetrate into the interior of cells is very low and b) by autophagy, the cells are able to capture foreign polymers, that penetrate their cytoplasm, in membrane-coated vesicles and thus, isolate these polymers from the processes occurring in the cell interior.