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exhibited a thermal melting temperature (Tm) value of +5.5 °C/modificationwhen hybridized against RNA resulting from a highlly preoganized RNA-like C-3’endo conformation (attributed to the combination of 2-thio modification and 2’-o-Mesubstituent). Oligonucleotides with this modification also exhibit betterhybridization discrimination for the wobble uracil-guanosine (U-G) base pairformation compared to the (8) Sites of Pyrimidine Modification normal uraciladenine(U-A) base pair. This selectivity is a result of weaker hydrogen bondingand increased steric bulk of the 2-thiocarbonyl group. 251OOC H 3NHNHoONSoONSo(9) (10)oO CH 3In contrast, the Pyrimidine modifications in 4-position with interestingproperties have been reported. 4-Thiopyrimidines (11,12) have beenincorporated into oligonucleotides with no significant negative effect onhybridization. However, recent studies have shown destabilization in the normaluraciladenin (U-A) base pair formation and stabilization of the wobble uracilguanosine (U-G) base pair for 4-thiouridine. A bicyclic 4-methoxy analog ofcytosine were shown to hybridize with both purine bases in DNA with thermalmelting temperature (Tm) values approximately equal to that of natural basepairs. Additionally, a fluorescent base has been incorporated intooligonucleotides and shown to enhance DNA-DNA duplex stability. 25248Pyrimidine…..