Synthesis, enzymatic stability and base-pairing properties of oligothymidylates containing thymidine dimers with different N-substituted guanidine linkages
Abstract
Reaction of 5′-amino-5′-deoxythymidine 1 with different S,S-dimethyl-N-substituted dithiocarbonimidates 2a–j afforded the N-substituted isothioureas 3a–j which, on further reaction with 3′-amino-3′-deoxythymidine 4 in the presence of AgNO3, led to thymidine dimers 5a–j with different N-substituted guanidine linkages. The dimer with a thiourea linkage (compound 9) was also prepared. Dimers 5a–h were incorporated at different positions in oligothymidylates by using phosphoramidite chemistry. Attempts to incorporate compounds 5i,j and 9 led to complex mixtures. 3′-Protected oligonucleotides showed somewhat higher stability to snake venom phosphodiesterase. Melting experiments revealed that the N-methylsulfonyl-substituted guanidine linkage best mimics the natural phosphodiester bridge. The fluorescence properties of oligonucleotides with dimer 5f were studied in view of its potential use as a non-radioactive label for DNA.
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