The present paper reports the determination of the configuration and Conformation of 1' -a-methoxy-2' -deoxy-2'-β-fluoro-2'-α-uracil-3',4' -o-isopropylidene-L-arabinoside obtained from silyla...The present paper reports the determination of the configuration and Conformation of 1' -a-methoxy-2' -deoxy-2'-β-fluoro-2'-α-uracil-3',4' -o-isopropylidene-L-arabinoside obtained from silylated uracil by using 13C-NMR and 2D-NMR.展开更多
Synthetic oligonucleotides including antisense oligonucleotides and siRNA have shown promising therapeutic potential.However,to realize the therapeutic potential of synthetic oligonucleotides,many obstacles have to be...Synthetic oligonucleotides including antisense oligonucleotides and siRNA have shown promising therapeutic potential.However,to realize the therapeutic potential of synthetic oligonucleotides,many obstacles have to be overcome,such as their poor biological stability,non-specific activity and inadequate cell membrane permeability.In this paper,the achievements by Lihe Zhang＇s group in the study of isonucleotide modified oligonucleotides and oligonucleotides conjugated with cell penetrating peptides are summarized.展开更多
Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was in...Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was investigated by thermal denaturation studies. Results Fourkinds of single isonucleoside containing oligonucleotides were synthesized. The results of thermaldenaturation showed that the existence of isonucleoside decreased the stability of duplex, and theeffect was more obvious when the isonucleoside was in the middle of the sequence. No obviousdifference was observed when 6'-OH of isonucleoside was free or was protected by allyl group.Conclusions The existence of isonucleoside in oli-gonucleotide makes chain twist and decreased thestability of duplex.展开更多
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 ant...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.展开更多
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 ant...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.展开更多
A series of 2'-purine and pyrimidine derivatives of 1' ,4'-anhy-dro-2'-deoxy-D-arabitol (1) and 1', 4'-anhydro-2'-deoxy-D-altritol (2) were synthesized regio- and stereo-selectively from D-...A series of 2'-purine and pyrimidine derivatives of 1' ,4'-anhy-dro-2'-deoxy-D-arabitol (1) and 1', 4'-anhydro-2'-deoxy-D-altritol (2) were synthesized regio- and stereo-selectively from D-sorbitol through some conversion in high yields.展开更多
文摘The present paper reports the determination of the configuration and Conformation of 1' -a-methoxy-2' -deoxy-2'-β-fluoro-2'-α-uracil-3',4' -o-isopropylidene-L-arabinoside obtained from silylated uracil by using 13C-NMR and 2D-NMR.
基金the National Natural Science Foundation of China.
文摘Novel bicyclic isonucleosides, 2′-deoxy-2′ -nucleobase-5′-deoxy-1′ , 4′ : 3′ , 6′ -dianhydro- D-mannitol 10a-10c, were synthesized from D-glucose. The computer-assisted molecular simu- lation indicated that the sugar conformations of compounds 10a-10c were restricted to N-con- formation.
基金National Natural Science Foundation (Grant No.20932001)the Ministry of Science and Technology (Grant No.2012CB720604)
文摘Synthetic oligonucleotides including antisense oligonucleotides and siRNA have shown promising therapeutic potential.However,to realize the therapeutic potential of synthetic oligonucleotides,many obstacles have to be overcome,such as their poor biological stability,non-specific activity and inadequate cell membrane permeability.In this paper,the achievements by Lihe Zhang＇s group in the study of isonucleotide modified oligonucleotides and oligonucleotides conjugated with cell penetrating peptides are summarized.
文摘Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was investigated by thermal denaturation studies. Results Fourkinds of single isonucleoside containing oligonucleotides were synthesized. The results of thermaldenaturation showed that the existence of isonucleoside decreased the stability of duplex, and theeffect was more obvious when the isonucleoside was in the middle of the sequence. No obviousdifference was observed when 6'-OH of isonucleoside was free or was protected by allyl group.Conclusions The existence of isonucleoside in oli-gonucleotide makes chain twist and decreased thestability of duplex.
基金supported by the National Natural Science Foundation of China(20932001)the Ministry of Science and Technology of China (2006AA02Z144,2009ZX09503)
文摘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.
文摘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.
基金Project (No. 970211006) supported by the Ministry of Science and Technology of China.
文摘A series of 2'-purine and pyrimidine derivatives of 1' ,4'-anhy-dro-2'-deoxy-D-arabitol (1) and 1', 4'-anhydro-2'-deoxy-D-altritol (2) were synthesized regio- and stereo-selectively from D-sorbitol through some conversion in high yields.
