Journal of the chemical society-perkin transactions 1 issue:14 pages:1567-1575
Reaction of 5'-amino-5'-deoxythymidine 1 with different SS-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.