As an approach to the study of the kind of chemical process that might have contributed to the origin of life, attempts have been made to develop purely chemical systems in which oligonucleotides self-replicate. Although performed oligonucleotides have been shown to facilitate the formation of their complements from activated mononucleotides, only a restricted range of oligomers are efficient templates and it will clearly be difficult to find a pair of complementary oligomers each of which will facilitate the formation of the other. Many of the difficulties facing the development of a self-replicating system could be overcome by using a pair of complementary substrate molecules that condense together more easily than ribonucleotides. It would also be helpful if each substrate molecule contained equal numbers of purine and pyrimidine bases as, otherwise, there is a tendency for purines to be overrepresented in the products. We have therefore explored the chemistry of 3'-amino-3'-deoxynucleotides and their dimers. We report here that the tetranucleoside triphosphoramidate GNHpCNHpGNHpCN3 acts as a template to catalyse the condensation of GNHpCNH2 and pGNHpCN3, forming further molecules of the template. The system is therefore autocatalytic, and in accordance with elementary theory the amount of product made increases with the square root of the template concentration.
BackgroundLinks between multimorbidity of allergic diseases and allergen sensitization are still under debate, especially in adults. This study aimed to establish a relationship between polysensitization and allergic multimorbidity in children and adults and the allergens involved in multimorbidity.Material and methodA cross-sectional multicentre study enrolled children aged 6–7 and 13–14 years and adults aged 20–44 years from a Polish national cohort. The diagnosis of allergic diseases was made by a physician. Skin prick tests to 13 allergens and serum IgE levels to 4 allergens were tested.ResultsAmong the 3856 participants, single disease (asthma, allergic rhinitis or atopic dermatitis) was diagnosed in 27.7% subjects and allergic multimorbidity in 9.3%. Allergic multimorbidity occurred more commonly in children than in adults (p < 0.01). Asthma or atopic dermatitis alone were not associated with polysensitization. Rhinitis and multimorbidity were associated with polysensitization. Allergic multimorbidity occurred in 2.2% of participants with negative skin prick tests, 9.8% of those with one positive prick test (SPT ≥ 3 mm) and 20.6% of polysensitized ones (p < 0.001). There was an increasing risk of multimorbidity depending on the number of positive prick tests for both SPT ≥ 3 mm (OR 9.6–16.5) and SPT ≥ 6 mm (OR 5.9–13.7). A statistically significant relationship was found between allergic multimorbidity and sensitization to cat and mite allergens.ConclusionsMultimorbidity is associated with polysensitization especially in children compared with adults in Polish population cohort. New insights into single disease patterns were found: bronchial asthma is the strongest risk factor for the development of multimorbidity in comparison with allergic rhinitis and atopic dermatitis.Electronic supplementary materialThe online version of this article (10.1186/s13601-019-0246-y) contains supplementary material, which is available to authorized users.
3'-amino-3'-deoxyuridine reacts with the nucleoside 5'-phosphorimidazolides in aqueous solution to give dinucleoside phosphoramidates. The reactions are one to two orders of magnitude faster than the corresponding reactions of uridine. In the presence of poly(C) or poly(dC) it is known that guanosine-5'-phosphorimidazolide does not condense efficiently or regiospecifically. However, the introduction of a methyl group at the 2-position of the imidazole ring leads to efficient synthesis of long 3'-5'-linked oligomers. The corresponding imidazole derivatives of 3'-amino-3'-deoxyguanosine-5'-phosphate both condense on these templates to give virtually identical families of products. Our results suggest that the intrinsically greater nucleophilicity of the amine groups will permit a much wider range of efficient template-directed syntheses with 3'-amino-3'-deoxynucleoside derivatives than with the corresponding derivatives of the parent nucleosides.
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