CHEMISTRY OF ALPHA-AMINONITRILES .17. OLI GO(NUCLEODIPEPTAMIDINIUM) SALTS

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 to wards finding such facts is to synthesize potential nucleic acid alter natives and to systematically compare their functional properties (bas e pairing, nonenzymic replication, sequence-specific catalysis) on the chemical level with those of RNA. Nucleic acid alternatives are chose n by the criterion of whether their potential for constitutional self- assembly without enzymes is judged by chemical reasoning to be compara ble to, or greater than, that of RNA. Alternatives which turn out to b e functional could have (but have not or may have only temporarily) be en chosen as a genetic system. Alternatives that are found to be non-f unctional can be dropped from the list of hypothetical RNA-competitors . Parallel to our work on nucleic acid alternatives based on hexopyran ose sugars, we have studied potential pairing systems that contain dip eptide derivatives instead of sugar phosphates as building blocks of t heir backbones. Oligo-nucleodipeptamidinium salts of the constitutiona l type shown in Figure 3 can be interpreted as representing oligomers of corresponding nucleodipeptide nitriles which, in turn, can be deriv ed from dipeptidic serine nitrifles. This paper summarizes our observa tions on the synthesis and properties of thyminyl- and adenyl-derivati ves 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 hydrolys is at pH-values above 4 (half life of dimers at pH = 6, 1-3 h at room temperature, ca. 30 h at 0 degrees C). Neither in UV-spectroscopically determined mixing curves (c approximate to 11 mu M, pH = 4, 4 degrees 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 pai ring. Although these observations must be considered as preliminary si nce they are rather limited with regard to structural variations, cond itions and observation methods, the properties observed for these mate rials discourage the view that such oligo-nucleodipeptamidinium salts might have been competitors to RNA.