Prebiotic condensations of mononucleotides by cyanamide and imidazole



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The condensation of mononucleotides was carried out in aqueous solutions at neutral pH in the presence of cyanamide or imidazole. To establish the role of carbodiimides in phosphodiester bond formation, preliminary studies were carried out with water-soluble dialkylcarbodiimides. In addition, condensations were carried out with cyanamide in anhydrous solvents such as pyridine. The results of these experiments showed that carbodiimides could promote such condensations, and suggested that cyanamide could also mediate such reactions in aqueous media. The condensation of mononucleotides in the presence of cyanamide was carried out at various concentrations and temperatures. The effect of templates such as polyornithine, deoxyribonucleic acid, and montmorillonite was also studied. The formation of oligodeoxyribonucleotides up to five units in length was observed. Radioactive mononucleotides were used in these studies and analysis was carried out by paper chromatography or column chromatography on DEAE-cellulose. In addition, standard oligodeoxyribonucleotides were synthesized and used in identification procedures. The role of imidazole in phosphodiester bond formation was also investigated. Formation of oligodeoxyribonucleotides by imidazole catalysis was observed. Two possible mechanisms for this condensation are given. In addition, imidazole derivatives such as histidine and 4-amino-5-imidazole carboxamide were used in order to study the effects of these substituted imidazole compounds on the condensation of mononucleotides. The use of modified mononucleotides such as adenosine-5'-phosphoramidate as a precursor for oligonucleotide formation was carried out. No phosphodiester bond formation was observed under the conditions employed. Cyclic polyphosphates such as sodium trimetaphosphate and sodium tetrametaphosphate were used as possible condensing agents. Experiments with aqueous solutions of thymidine-5'-monophosphate showed that the cyclic polyphosphates did not promote internucleotidic linkage.