In order to prepare pyrimidine nucleoside-peptide conjugate concisely, we developed a one-pot synthetic strategy. Started from uridine, 5-S-acetyl-thiomethyl-2＇,3 ＇-di-O-isopropylidene-uridine （4） was synthesized as the key intermediate in four steps. Under acidic condition, compound 4 was deprotected and reacted with PySS-R （8, 12, 15, Py = 2-pyridyl, R = amino acid or peptide） in one pot to form uridine conjugates （9, 13, 2） with disulfide bond as linker.
Stability, specificity, and pharmacokinetic properties are some of the challenges facing RNAi therapeutics. In this review, the progresses in chemically modified siRNAs and siRNA conjugates are summarized. The proper modification of siRNA with nucleoside analogues, construction of siRNA conjugates, and reliable prediction of the property based on those strategies for a given siRNA sequence would certainly be an essential part of the solution to these challenges.
