CpG oligodeoxynucleotides （CpG ODN） as adjuvant have been extensively studied in recent years. Phosphodiester CpG ODN （PO CpG ODN） can perfectly mimic bacterial DNA in enhancing immune response but are vulnerable ...CpG oligodeoxynucleotides （CpG ODN） as adjuvant have been extensively studied in recent years. Phosphodiester CpG ODN （PO CpG ODN） can perfectly mimic bacterial DNA in enhancing immune response but are vulnerable to nucleases in vivo. This study aimed to evaluate the immunostimulatory potential arid safety of phosphodiester CpG ODN encapsulated in nonphospholipid liposomes. BALB/c mice were immunized intramuscularly with different formulations of liposomes, CpG ODN and hepatitis B surface antigen （HBsAg）. The results demonstrated that the encapsulated PO CpG ODN were protected against rapid degradation in vivo and retained their adjuvant activity. PO CpG ODN encapsulated with HBsAg in liposomes induced strong Th1-biased or Th1/Th2 mixed humoral immune response in mice with the magnitude similar to their phosphothioate equivalent in the same formulation. High IFN-gamma production induced by this formulation confirmed the generation of strong cellular immune response. Additionally, co-delivery of HBsAg arid PO CpG ODN improved the immune response over that obtained with separate delivery. Safety experiment showed that liposome-encapsulaed PO CpG ODN and HBsAg caused mild systemic and moderate local adverse reaction. In conclusion, our data shows that PO CpG ODN encapsulated in liposomes fully exhibit their Th1-type adjuvant activity arid act as a potential adjuvant for vaccines.展开更多
We aimed to explore the role of chitosan-based metal complexes in catalyzing the hydrolysis of phosphodiesters To this end, we performed detailed studies on the kinetics of the chitosan copper complex （CSCu）-catalyz...We aimed to explore the role of chitosan-based metal complexes in catalyzing the hydrolysis of phosphodiesters To this end, we performed detailed studies on the kinetics of the chitosan copper complex （CSCu）-catalyzed hydrolysis of bis（4-nitrophenol） phosphate （BNPP） in Tris-H＋ buffer and in an organic solvent. A significant enhancement in the rate of reaction （up to 3 X 105-fold acceleration） was observed at pH 8.0 （25 ℃）. The pH depend- ence of BNPP hydrolysis at pH 5.5-9.5 and the UV spectra revealed that the copper-bounded water molecules un- derwent deprotonation to form the active catalytic species CSCu-OH. The kinetic behavior of BNPP catalytic hydrolysis in the Tris-H＋ buffer was consistent with that predicted by the Michaelis-Menten kinetics model. An in-ramolecular nucleophilic attack by the copper-bonded hydroxide group on the same activated phosphodiester substrate was proposed as the catalytic mechanism for CSCu-catalyzed reaction system. The results of DNA binding and cleavage experiments indicated electrostatic binding mode of CSCu to DNA as well as the strong capability of CSCu to disturb the supercoiled strand of DNA and cleave it to nicked circular form.展开更多
The catalytic hydrolysis of bis（4-nitrophenyl）phosphate （BNPP） by lanthanum（Ⅲ） ion in the presence of amino-alcoholic ligands： diethanolamine （DEA） and triethanolamine （TEA）, was investigated kinetically a...The catalytic hydrolysis of bis（4-nitrophenyl）phosphate （BNPP） by lanthanum（Ⅲ） ion in the presence of amino-alcoholic ligands： diethanolamine （DEA） and triethanolamine （TEA）, was investigated kinetically at 30 ℃. The results indicated that the dinuclear dihydroxo complexes formed by lanthanum（Ⅲ） ion with aminoalcoholic ligands might be the catalytically active species which catalyze the hydrolysis of BNPP to different extents and the catalytic mechanism was believed to involve the synergism of double Lewis acid activation of the substrate and an intramolecular nucleophilic attack of a bridging oxo ligand.展开更多
A new fluorescent probe for lead ions,p-nitrophenyl 3H-phenoxazin-3-one-7-yl phosphoric acid (NPPA), has been synthesized by linking resorufin (serving as a fluorophore and electron acceptor) to p-nitrophenol (serving...A new fluorescent probe for lead ions,p-nitrophenyl 3H-phenoxazin-3-one-7-yl phosphoric acid (NPPA), has been synthesized by linking resorufin (serving as a fluorophore and electron acceptor) to p-nitrophenol (serving as a fluorescence quencher and electron donor) through phosphodiester bonds. When NPPA was irradiated with light, intramolecular fluorescence self-quenching took place due to the PET (photoinduced electron transfer) from the donor to the acceptor. However, upon addition of PbII, the phosphate ester bonds in the probe were cleaved and the fluorophore was released, accompanying the retrievement of fluorescence.展开更多
Two new dicopper（II） complexes [Cu2L（OAc）2]（ClO4）·H2O （1） and [Cu2L（BPP）2]-（ClO4） （2） using an asymmetric dinucleating ligand HL and auxiliary ligands such as acetate （OAc） and bisphenyl phosphate...Two new dicopper（II） complexes [Cu2L（OAc）2]（ClO4）·H2O （1） and [Cu2L（BPP）2]-（ClO4） （2） using an asymmetric dinucleating ligand HL and auxiliary ligands such as acetate （OAc） and bisphenyl phosphate （BPP） have been synthesized and characterized by elemental analysis, IR and single-crystal X-ray diffraction. Complex 1 crystallizes as blue single crystals that belong to the triclinic crystal system and Pī space group, while complex 2 crystallizes in a monoclinic P21/c space group. Single-crystal X-ray diffraction analysis reveals that the two copper ions in complexes 1 and 2 reside within the adjacent ligand compartments and are bridged by the endogenous phenoxo-O from ligand L and the introduction of two desired exogenous carboxylates or phosphates in the bidentate μ-1,3-bridged mode. The coordination geometries of Cu（1） and Cu（2） are both distorted square pyramids.展开更多
Artificial nucleic acid cleavage agents have attracted close attention because they play important roles in biochemistry and molecular biology. According to the cleavage mechanism of nucleic acid, they are divided int...Artificial nucleic acid cleavage agents have attracted close attention because they play important roles in biochemistry and molecular biology. According to the cleavage mechanism of nucleic acid, they are divided into three types, namely free radical, phosphodiester bond hydrolysis and elimination cleavage agents. In this review, a series of cleavage agents, including the site- and sequence-specific ones, are illustrated, and some suggestions for the future researches in this field are also put forward.展开更多
The interaction of Cu^2＋ complex of N,N＇-bis（2-aminoethyl）-2,6-pyridinedicarboxamide （BAP） with DNA was studied by agarose gel electrophoresis analysis. The results indicate that the BAP-Cu^2＋ complex can promo...The interaction of Cu^2＋ complex of N,N＇-bis（2-aminoethyl）-2,6-pyridinedicarboxamide （BAP） with DNA was studied by agarose gel electrophoresis analysis. The results indicate that the BAP-Cu^2＋ complex can promote the cleavage of phosphodiester bond of supercoiled DNA at physiological condition, which is 3.2 × 10^6 times higher than DNA natural degradation. A hydrolytic cleaving mechanism through the cooperation of copper ions and functional amino groups was proposed.展开更多
文摘CpG oligodeoxynucleotides （CpG ODN） as adjuvant have been extensively studied in recent years. Phosphodiester CpG ODN （PO CpG ODN） can perfectly mimic bacterial DNA in enhancing immune response but are vulnerable to nucleases in vivo. This study aimed to evaluate the immunostimulatory potential arid safety of phosphodiester CpG ODN encapsulated in nonphospholipid liposomes. BALB/c mice were immunized intramuscularly with different formulations of liposomes, CpG ODN and hepatitis B surface antigen （HBsAg）. The results demonstrated that the encapsulated PO CpG ODN were protected against rapid degradation in vivo and retained their adjuvant activity. PO CpG ODN encapsulated with HBsAg in liposomes induced strong Th1-biased or Th1/Th2 mixed humoral immune response in mice with the magnitude similar to their phosphothioate equivalent in the same formulation. High IFN-gamma production induced by this formulation confirmed the generation of strong cellular immune response. Additionally, co-delivery of HBsAg arid PO CpG ODN improved the immune response over that obtained with separate delivery. Safety experiment showed that liposome-encapsulaed PO CpG ODN and HBsAg caused mild systemic and moderate local adverse reaction. In conclusion, our data shows that PO CpG ODN encapsulated in liposomes fully exhibit their Th1-type adjuvant activity arid act as a potential adjuvant for vaccines.
基金Project supported by the National Natural Science Foundation of China （Nos. 20403002, 20773008）, the Beijing Novel Program （No. 2008B 12） and the National High-Tech R＆D Program （No. 2007AA05Z146）.
文摘We aimed to explore the role of chitosan-based metal complexes in catalyzing the hydrolysis of phosphodiesters To this end, we performed detailed studies on the kinetics of the chitosan copper complex （CSCu）-catalyzed hydrolysis of bis（4-nitrophenol） phosphate （BNPP） in Tris-H＋ buffer and in an organic solvent. A significant enhancement in the rate of reaction （up to 3 X 105-fold acceleration） was observed at pH 8.0 （25 ℃）. The pH depend- ence of BNPP hydrolysis at pH 5.5-9.5 and the UV spectra revealed that the copper-bounded water molecules un- derwent deprotonation to form the active catalytic species CSCu-OH. The kinetic behavior of BNPP catalytic hydrolysis in the Tris-H＋ buffer was consistent with that predicted by the Michaelis-Menten kinetics model. An in-ramolecular nucleophilic attack by the copper-bonded hydroxide group on the same activated phosphodiester substrate was proposed as the catalytic mechanism for CSCu-catalyzed reaction system. The results of DNA binding and cleavage experiments indicated electrostatic binding mode of CSCu to DNA as well as the strong capability of CSCu to disturb the supercoiled strand of DNA and cleave it to nicked circular form.
基金Project supported by the National Natural Science Foundation of China （Nos. 20173038, 20107004）.
文摘The catalytic hydrolysis of bis（4-nitrophenyl）phosphate （BNPP） by lanthanum（Ⅲ） ion in the presence of amino-alcoholic ligands： diethanolamine （DEA） and triethanolamine （TEA）, was investigated kinetically at 30 ℃. The results indicated that the dinuclear dihydroxo complexes formed by lanthanum（Ⅲ） ion with aminoalcoholic ligands might be the catalytically active species which catalyze the hydrolysis of BNPP to different extents and the catalytic mechanism was believed to involve the synergism of double Lewis acid activation of the substrate and an intramolecular nucleophilic attack of a bridging oxo ligand.
基金supported by the NNSF of China(No.20175031,No.20035010)
文摘A new fluorescent probe for lead ions,p-nitrophenyl 3H-phenoxazin-3-one-7-yl phosphoric acid (NPPA), has been synthesized by linking resorufin (serving as a fluorophore and electron acceptor) to p-nitrophenol (serving as a fluorescence quencher and electron donor) through phosphodiester bonds. When NPPA was irradiated with light, intramolecular fluorescence self-quenching took place due to the PET (photoinduced electron transfer) from the donor to the acceptor. However, upon addition of PbII, the phosphate ester bonds in the probe were cleaved and the fluorophore was released, accompanying the retrievement of fluorescence.
文摘Two new dicopper（II） complexes [Cu2L（OAc）2]（ClO4）·H2O （1） and [Cu2L（BPP）2]-（ClO4） （2） using an asymmetric dinucleating ligand HL and auxiliary ligands such as acetate （OAc） and bisphenyl phosphate （BPP） have been synthesized and characterized by elemental analysis, IR and single-crystal X-ray diffraction. Complex 1 crystallizes as blue single crystals that belong to the triclinic crystal system and Pī space group, while complex 2 crystallizes in a monoclinic P21/c space group. Single-crystal X-ray diffraction analysis reveals that the two copper ions in complexes 1 and 2 reside within the adjacent ligand compartments and are bridged by the endogenous phenoxo-O from ligand L and the introduction of two desired exogenous carboxylates or phosphates in the bidentate μ-1,3-bridged mode. The coordination geometries of Cu（1） and Cu（2） are both distorted square pyramids.
文摘Artificial nucleic acid cleavage agents have attracted close attention because they play important roles in biochemistry and molecular biology. According to the cleavage mechanism of nucleic acid, they are divided into three types, namely free radical, phosphodiester bond hydrolysis and elimination cleavage agents. In this review, a series of cleavage agents, including the site- and sequence-specific ones, are illustrated, and some suggestions for the future researches in this field are also put forward.
基金Project supported by the National Natural Science Foundation of China （No. 20372032） and the Analytical Foundation of Nanjing University.
文摘The interaction of Cu^2＋ complex of N,N＇-bis（2-aminoethyl）-2,6-pyridinedicarboxamide （BAP） with DNA was studied by agarose gel electrophoresis analysis. The results indicate that the BAP-Cu^2＋ complex can promote the cleavage of phosphodiester bond of supercoiled DNA at physiological condition, which is 3.2 × 10^6 times higher than DNA natural degradation. A hydrolytic cleaving mechanism through the cooperation of copper ions and functional amino groups was proposed.
