SYNTHESIS, ENZYMATIC STABILITY AND BASE-PAIRING PROPERTIES OF OLIGOTHYMIDYLATES CONTAINING THYMIDINE DIMERS WITH DIFFERENT N-SUBSTITUTED GUANIDINE LINKAGES

Reaction of 5'-amino-5'-deoxythymidine 1 with different SS-dimethyl-N- substituted dithiocarbonimidates 2a-j afforded the N-substituted isoth ioureas 3a-j which, on further reaction with 3'-amino-3'-deoxythymidin e 4 in the presence of AgNO3, led to thymidine dimers 5a-j with differ ent N-substituted guanidine linkages. The dimer with a thiourea linkag e (compound 9) was also prepared. Dimers 5a-h were incorporated at dif ferent positions in oligothymidylates by using phosphoramidite chemist ry. Attempts to incorporate compounds 5i,j and 9 led to complex mixtur es. 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-radi oactive label for DNA.