2-Thio-Uridine (s2U)

- The effect of 2-thiouridine on sugar conformation and RNA duplex thermodynamics has been well documented (1,2). The presence of the 2-sulfur modification stabilizes the 3’-endo sugar conformation at the nucleoside and nucleotide level (1). Wobble base pair specificity can also be improved by substituting 2-thiouridine for uridine. Testa and co-workers (2) have shown the at S2U favors S2U-A pairing more than S2U-G pairing, and more than U favors U-A relative to U-G. The sulfur modification improves specificity while retaining other key uridine activities.
In addition, thiolated uridine has been shown to improve the rate and fidelity of both nonenzymatic (3) and ribozyme (4) catalyzed nucleotide addition in RNA synthesis.

References
1. Kumar, R.K.; Davis, D.R. Nuc. Acid. Res. 1997, 25(6), 1272-1280.
2. Testa, S.M.; Disney, M.D.; Turner, D.H.; Kierzek, R. Biochem. 1999, 38, 16655-16662.
3. Heuberger, B.D.; Pal, A.; Del Frate, F.; Topkar, V.V.; Szostak, J.W. J. Am. Chem. Soc., 2015, 137 (7), pp 2769–2775.
4. Prywes, N.; Michaels, Y.S.; Pal, A.; Oh, S.S., Szostak, J.W. Chem. Commun. 2016. 52, 6529-6532.
5. a) Kumar, R.K.; Davis, D.R. J. Org. Chem.1995, 60, 7726-7727. b) Gait, M.J. Oligonucleotide Synthesis-A Practical Approach 1990, Oxford University Press, London.