Chemie von α-Aminonitrilen. XVII. Oligo(nukleodipeptamidinium)-Salze

Experiments directed towards a chemical etiology of nucleic acids aim at uncovering facts that may help us to rationalize Nature's choice of the RNA structure in the evolution of a genetic system. A strategy towards finding such facts is to synthesize potential nucleic acid alternatives and to systematically compare their functional properties (base pairing, nonenzymic replication, sequence- specific catalysis) on the chemical level with those of RNA. Nucleic acid alternatives are chosen by the criterion of whether their potential for constitutional self-assembly without enzymes is judged by chemical reasoning to be comparable to, or greater than, that of RNA. Alternatives which turn out to be functional could have (but have not or may have only temporarily) been chosen as a genetic system. Alternatives that are found to be non-functional can be dropped from the list of hypothetical RNA-competitors. Parallel to our work on nucleic acid alternatives based on hexopyranose sugars, we have studied potential pairing systems that contain dipeptide derivatives instead of sugar phosphates as building blocks of their backbones. Oligo-nucleodipeptamidinium salts of the constitutional type shown in Figure 3 can be interpreted as representing oligomers of corresponding nucleodipeptide nitriles which, in turn, can be derived from dipeptidic serine nitriles. This paper summarizes our observations on the synthesis and properties of thyminyl- and adenyl-derivatives of (L)-oligo-nucleodipeptamidinium salts (up to decamers) belonging to the constitutional type shown in Figures 9 and 10. Such oligomers are soluble in aqueous medium but turn out to be sensitive to hydrolysis at pH-values above 4 (half life of dimers at pH = 6, 1-3 h at room temperature, ca. 30 h at 0 °C). Neither in UV-spectroscopically determined mixing curves (c » 11 pM, pH = 4, 4 °C, 1 M NaCl) of mixtures of hexamers that contain complementary bases, nor in CD- spectra of (1 : 1) mixtures of the corresponding decamers (similar conditions) could we observe signs of adenine-thymine base pairing. Although these observations must be considered as preliminary since they are rather limited with regard to structural variations, conditions and observation methods, the properties observed for these materials discourage the view that such oligo-nucleodipeptamidinium salts might have been competitors to RNA. EINLEITUNG »Sie (die Naturstoffe) sind das Ergebnis einer drei Milliarden Jahre dauernden Entwicklung der lebe