Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of e...Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.展开更多
Fifteen novel 2-（3-oxobenzo[d]isothiazol-2（3H）-yl）ethyl benzoates were synthesi- zed by the condensation of 2-（2-hydroxyethyl）benzo[d]isothiazol-3（2H）-one with substituted benzoic acids in dichloromethane. All...Fifteen novel 2-（3-oxobenzo[d]isothiazol-2（3H）-yl）ethyl benzoates were synthesi- zed by the condensation of 2-（2-hydroxyethyl）benzo[d]isothiazol-3（2H）-one with substituted benzoic acids in dichloromethane. All the compounds were characterized by elemental analysis, IR, ESI-MS and 1H NMR. The crystal structures for 2-（2-hydroxyethyl）benzo[d]isothiazol-3（2H）-one （2） and 2-（3-oxobenzo[d]isothiazol-2（3H）-yl）ethyl 2-methoxybenzoate （30） have been determined by X-ray crystal structure analysis. Compound 2 （C9H9NO2S） crystallizes in the monoclinic system, space group Pn with a = 10.552（3）, b = 7.849（2）, c = 10.765（4） A, β = 103.128（4）°, V= 868.3（5） A3, Mr = 195.24, Dc = 1.493 Mg.m-3, μ = 0.33 mm-1, F（000） = 408, Z = 4, R= 0.0314 and wR= 0.0628. Compound 30 （C17H15NO4S） crystallizes in the triclinic system, space group P1 with a = 8.028（2）, b = 9.300（2）, c = 10.430（3）A, V= 752.1（3）A3, Mr = 329.36, D,= 1.454 Mg.m-3, p = 0.24 mm-1, F（000） = 344, Z = 2, R = 0.0377 and wR = 0.0904. The preliminary biological test indicated that the title compounds show better growth inhibitory activity against the gram-positive bacteria than the gram-negative bacteria.展开更多
The molecule with Th symmetry is rare.A dodecahedrane-like molecule C12H12B8 with uncommon Th symmetry has been reported here.Density functional calculations and minimization techniques have been employed to character...The molecule with Th symmetry is rare.A dodecahedrane-like molecule C12H12B8 with uncommon Th symmetry has been reported here.Density functional calculations and minimization techniques have been employed to characterize its structural and electronic properties.Its geometry,electronic properties,vibrational frequencies and heat of formation have been calculated at the B3LYP/6-311＋G（d,p） level of theory.The absence of imaginary vibrational frequency confirms that it corresponds to true minimum on the potential energy hypersurface.Its vibrational bands in the IR intensity have been discussed and compared with future experimental identification.At the B3LYP/6-311＋G（d,p） level,the heat of formation has been calculated to be 720.9 kJ mol^-1 using the isodesmic reaction.According to this value,it is a potential high energy density molecule.展开更多
基金supported by the General Program of the National Natural Science Foundation of China[No.31570162]the National Key Research Program[No.2016YFC1200200].
文摘Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.
基金Supported by the National Natural Science Foundation of China (No. 20962007)
文摘Fifteen novel 2-（3-oxobenzo[d]isothiazol-2（3H）-yl）ethyl benzoates were synthesi- zed by the condensation of 2-（2-hydroxyethyl）benzo[d]isothiazol-3（2H）-one with substituted benzoic acids in dichloromethane. All the compounds were characterized by elemental analysis, IR, ESI-MS and 1H NMR. The crystal structures for 2-（2-hydroxyethyl）benzo[d]isothiazol-3（2H）-one （2） and 2-（3-oxobenzo[d]isothiazol-2（3H）-yl）ethyl 2-methoxybenzoate （30） have been determined by X-ray crystal structure analysis. Compound 2 （C9H9NO2S） crystallizes in the monoclinic system, space group Pn with a = 10.552（3）, b = 7.849（2）, c = 10.765（4） A, β = 103.128（4）°, V= 868.3（5） A3, Mr = 195.24, Dc = 1.493 Mg.m-3, μ = 0.33 mm-1, F（000） = 408, Z = 4, R= 0.0314 and wR= 0.0628. Compound 30 （C17H15NO4S） crystallizes in the triclinic system, space group P1 with a = 8.028（2）, b = 9.300（2）, c = 10.430（3）A, V= 752.1（3）A3, Mr = 329.36, D,= 1.454 Mg.m-3, p = 0.24 mm-1, F（000） = 344, Z = 2, R = 0.0377 and wR = 0.0904. The preliminary biological test indicated that the title compounds show better growth inhibitory activity against the gram-positive bacteria than the gram-negative bacteria.
基金supported by the Natural Science Foundation of Shandong Province (No. ZR2011BM022)
文摘The molecule with Th symmetry is rare.A dodecahedrane-like molecule C12H12B8 with uncommon Th symmetry has been reported here.Density functional calculations and minimization techniques have been employed to characterize its structural and electronic properties.Its geometry,electronic properties,vibrational frequencies and heat of formation have been calculated at the B3LYP/6-311＋G（d,p） level of theory.The absence of imaginary vibrational frequency confirms that it corresponds to true minimum on the potential energy hypersurface.Its vibrational bands in the IR intensity have been discussed and compared with future experimental identification.At the B3LYP/6-311＋G（d,p） level,the heat of formation has been calculated to be 720.9 kJ mol^-1 using the isodesmic reaction.According to this value,it is a potential high energy density molecule.
