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.
Antisense oligonucleotides(ASONs) and siRNAs have been applied extensively for the regulation of cellular and viral gene expression,and RNAi is currently one of the most promising new approaches for anti-tumor and anti-viral therapy.In order to improve bioactivity properties and physicochemical properties of siRNA,we synthesized a novel class of ASONs II-VII incorporated with amino-isonucleoside(isoA1 and isoA2) for investigation on basic physicochemical properties.Then we designed amino-isonucleoside(isoA1,isoA2 and isoT1) incorporated siRNA 2-7.Some meaningful results have been obtained from the physicochemical property experiments in ASONs.In RNAi potency experiments,we investigated RNAi potency of each strand of the siRNA.These amino-isonucleosides incorporated siRNAs showed promising bioactivity properties and had position specificity.Reduced off target effect from sense strand loading in siRNA application was observed.
WANG FangCHEN YueHUANG YeJIN Hong-WeiZHANG Liang-RenYANG Zhen-JunZHANG Li-He
Antisense oligonucleotides(ASONs) and siRNAs have been applied extensively for the regulation of cellular and viral gene expression,and RNAi is currently one of the most promising new approaches for anti-tumor and anti-viral therapy.In order to improve bioactivity properties and physicochemical properties of siRNA,we synthesized a novel class of ASONs II-VII incorporated with amino-isonucleoside(isoA1 and isoA2) for investigation on basic physicochemical properties.Then we designed amino-isonucleoside(isoA1,isoA2 and isoT1) incorporated siRNA 2-7.Some meaningful results have been obtained from the physicochemical property experiments in ASONs.In RNAi potency experiments,we investigated RNAi potency of each strand of the siRNA.These amino-isonucleosides incorporated siRNAs showed promising bioactivity properties and had position specificity.Reduced off target effect from sense strand loading in siRNA application was observed.
WANG FangCHEN YueHUANG YeJIN Hong-WeiZHANG Liang-RenYANG Zhen-JunZHANG Li-He
