Aim To study the binding behavior between human serum albumin （HSA） and phosphorothioate oligodeoxynucleotide （PS- ODN） and the effects of bivalent cations on the interaction. Methods Surface plasma resonance, cir...Aim To study the binding behavior between human serum albumin （HSA） and phosphorothioate oligodeoxynucleotide （PS- ODN） and the effects of bivalent cations on the interaction. Methods Surface plasma resonance, circular dichroism and fluorescence experiments were conducted. Results （ 1 ） the binding ability was decreased along with the increase of pH; （2） Zn^2＋and Ni^2＋ enhanced the interaction between PS-ODN and HSA; （3） Upon PS-ODN binding, the conformation of HSA was changed with an increase of β - sheet. Conclusion The results provide experimental evidences to the hypothesis that PS-ODN binds with HSA in the positive potential region, and histidine residues located in the region play a crucial rule in the interaction.展开更多
反基因疗法是通过寡核苷酸链在dsD N A与蛋白质的结合部位形成三链结构来抑制基因的转录,达到治疗肿瘤的效果。由于天然寡核苷酸链存在易被核酸酶消化、半衰期短、稳定性差、不易透过细胞膜、以及安全性等问题,制约了反基因技术的发展...反基因疗法是通过寡核苷酸链在dsD N A与蛋白质的结合部位形成三链结构来抑制基因的转录,达到治疗肿瘤的效果。由于天然寡核苷酸链存在易被核酸酶消化、半衰期短、稳定性差、不易透过细胞膜、以及安全性等问题,制约了反基因技术的发展。近年来研制出的硫代寡核苷酸链、肽核酸、锁核酸等修饰物使寡核苷酸链的性能得到了很大提高,为反基因疗法的临床广泛应用提供了理论和实践依据。本文就寡核苷酸链在肿瘤及基因疗法中的运用新近展作一综述。展开更多
AIM:To explore the membrane permeability, enzyme tolerance, and stability of phosphorothioate oligodeoxynucleotide(P ODN) which can inhibit cerebral thrombosis.METHODS:(1)Oligodeoxynucleotide was synthesized with phos...AIM:To explore the membrane permeability, enzyme tolerance, and stability of phosphorothioate oligodeoxynucleotide(P ODN) which can inhibit cerebral thrombosis.METHODS:(1)Oligodeoxynucleotide was synthesized with phosphoramidite method in solid phase,3’ end was modified with thiophosphoter.(2)Uptake and subcellular distribution of P ODN.P ODN was given directly.We observed total uptake rate of P ODN by ECV304 cells and subcellular distribution of P ODN.RESULTS:(1)ECV cells uptake more P ODN with increase of concentration,the uptake rate was about 10.8%-11.9%.(2)Subcellular distribution of P ODN:P ODN was mainly distributed in nucleus especially nucleus sediments(69.3%-77.2%)(P< 0.05).CONCLUSION:P ODN suppressing cerebral thrombosis has favorable transmembrane ability,enzyme resistance and stability.展开更多
基金This work was supported by the National Natural Science Foundation of China(20472007).
文摘Aim To study the binding behavior between human serum albumin （HSA） and phosphorothioate oligodeoxynucleotide （PS- ODN） and the effects of bivalent cations on the interaction. Methods Surface plasma resonance, circular dichroism and fluorescence experiments were conducted. Results （ 1 ） the binding ability was decreased along with the increase of pH; （2） Zn^2＋and Ni^2＋ enhanced the interaction between PS-ODN and HSA; （3） Upon PS-ODN binding, the conformation of HSA was changed with an increase of β - sheet. Conclusion The results provide experimental evidences to the hypothesis that PS-ODN binds with HSA in the positive potential region, and histidine residues located in the region play a crucial rule in the interaction.
文摘反基因疗法是通过寡核苷酸链在dsD N A与蛋白质的结合部位形成三链结构来抑制基因的转录,达到治疗肿瘤的效果。由于天然寡核苷酸链存在易被核酸酶消化、半衰期短、稳定性差、不易透过细胞膜、以及安全性等问题,制约了反基因技术的发展。近年来研制出的硫代寡核苷酸链、肽核酸、锁核酸等修饰物使寡核苷酸链的性能得到了很大提高,为反基因疗法的临床广泛应用提供了理论和实践依据。本文就寡核苷酸链在肿瘤及基因疗法中的运用新近展作一综述。
文摘AIM:To explore the membrane permeability, enzyme tolerance, and stability of phosphorothioate oligodeoxynucleotide(P ODN) which can inhibit cerebral thrombosis.METHODS:(1)Oligodeoxynucleotide was synthesized with phosphoramidite method in solid phase,3’ end was modified with thiophosphoter.(2)Uptake and subcellular distribution of P ODN.P ODN was given directly.We observed total uptake rate of P ODN by ECV304 cells and subcellular distribution of P ODN.RESULTS:(1)ECV cells uptake more P ODN with increase of concentration,the uptake rate was about 10.8%-11.9%.(2)Subcellular distribution of P ODN:P ODN was mainly distributed in nucleus especially nucleus sediments(69.3%-77.2%)(P< 0.05).CONCLUSION:P ODN suppressing cerebral thrombosis has favorable transmembrane ability,enzyme resistance and stability.
基金中国博士后科学基金(No.20060390735)广东省生物工程药物重点实验室基金(No.51206001)+1 种基金Supported by the Postdoctoral Science Foundation of China(No.20060390735)Foundation for key Laboratory of Bioengineering Drug of Guangdong Province (No.51206001)
