Bacterial leaf blight(BLB)is a devastating disease of rice with the potential to reduce yield by up to 70%.In this study,we investigated the genetic foundation of Xa21-mediated resistance to BLB infection in seven dif...Bacterial leaf blight(BLB)is a devastating disease of rice with the potential to reduce yield by up to 70%.In this study,we investigated the genetic foundation of Xa21-mediated resistance to BLB infection in seven different rice varieties from Myanmar.The varieties exhibited a variable phenotypic response at 14 d after infection(DAI)by Xoo strains K1 and K3a,among which,the variety Kayin Ma was classified as a moderately resistant(MR)variety,expressing Xa2,Xa4,xa5,xa13,and Xa21 genes.展开更多
Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug ...Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug design framework, Drug CAMD, that integrates a deep learning model with a mixed-integer nonlinear programming model is used for designing drug candidates. Within this framework, a virtual chemical library is specifically tailored to inhibit Factor Xa. To further filter and narrow down the lead compounds from the designed compounds, comprehensive approaches involving molecular docking,binding pose metadynamics(BPMD), binding free energy calculations, and enzyme activity inhibition analysis are utilized. To maximize efficiency in terms of time and resources, molecules for in vitro activity testing are initially selected from commercially available portions of customized virtual chemical libraries. In vitro studies assessing inhibitor activities have confirmed that the compound EN300-331859shows potential Factor Xa inhibition, with an IC_(50)value of 34.57 μmol·L^(-1). Through in silico molecular docking and BPMD, the most plausible binding pose for the EN300-331859-Factor Xa complex are identified. The estimated binding free energy values correlate well with the results obtained from biological assays. Consequently, EN300-331859 is identified as a novel and effective sub-micromolar inhibitor of Factor Xa.展开更多
In marker-assisted breeding for bacterial blight(BB) resistance in rice, three major resistance genes, viz., Xa21, xa13 and xa5, are routinely deployed either singly or in combinations. As efficient and functional mar...In marker-assisted breeding for bacterial blight(BB) resistance in rice, three major resistance genes, viz., Xa21, xa13 and xa5, are routinely deployed either singly or in combinations. As efficient and functional markers are yet to be developed for xa13 and xa5, we have developed simple PCR-based functional markers for both the genes. For xa13, we designed a functional PCR-based marker, xa13-prom targeting the In Del polymorphism in the promoter of candidate gene Os8N3 located on chromosome 8 of rice. With respect to xa5, a multiplex-PCR based functional marker system, named xa5 FM, consisting of two sets of primer pairs targeting the 2-bp functional nucleotide polymorphism in the exon II of the gene TFIIA5(candidate for xa5), has been developed. Both xa13-prom and xa5 FM can differentiate the resistant and susceptible alleles for xa13 and xa5, respectively, in a co-dominant fashion. Using these two functional markers along with the already reported functional PCR-based marker for Xa21(p TA248), we designed a single-tube multiplex PCR based assay for simultaneous detection of all the three major resistance genes and demonstrated the utility of the multiplex marker system in a segregating population.展开更多
The title compound （zifaxaban 2, C20HI6C1N3O4S, Mr = 429.87） was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a...The title compound （zifaxaban 2, C20HI6C1N3O4S, Mr = 429.87） was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a = 5.7900（12）, b = 13.086（3）, c = 12.889（3） A, β= 100.86（3）°, V = 959.1（3） ）k3, Z = 2, Dc= 1.489 g/cm3, F（000） = 444,μ= 0.342 mm-l, the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections （I 〉 20（I）. The absolute configuration of the stereogenic center in the title compound was confirmed to be S by single-crystal X-ray diffraction. Four existing intermolecular hydrogen bonds help to stabilize the lattice and the molecule in the lattice to adopt an L-shape conformation. Zifaxaban was slightly more active than rivaroxaban 1 in in vitro assay against human FXa and therefore is promising as a drug candidate.展开更多
基金funded by the Basic Science Research Program of the Ministry of Education’s National Research Foundation of Korea (Grant No.RS-2023-00245922)。
文摘Bacterial leaf blight(BLB)is a devastating disease of rice with the potential to reduce yield by up to 70%.In this study,we investigated the genetic foundation of Xa21-mediated resistance to BLB infection in seven different rice varieties from Myanmar.The varieties exhibited a variable phenotypic response at 14 d after infection(DAI)by Xoo strains K1 and K3a,among which,the variety Kayin Ma was classified as a moderately resistant(MR)variety,expressing Xa2,Xa4,xa5,xa13,and Xa21 genes.
基金financial supports of the National Natural Science Foundation of China (22078041, 22278053,22208042)Dalian High-level Talents Innovation Support Program (2023RQ059)“the Fundamental Research Funds for the Central Universities (DUT20JC41, DUT22YG218)”。
文摘Small-molecule drugs are essential for maintaining human health. The objective of this study is to identify a molecule that can inhibit the Factor Xa protein and be easily procured. An optimization-based de novo drug design framework, Drug CAMD, that integrates a deep learning model with a mixed-integer nonlinear programming model is used for designing drug candidates. Within this framework, a virtual chemical library is specifically tailored to inhibit Factor Xa. To further filter and narrow down the lead compounds from the designed compounds, comprehensive approaches involving molecular docking,binding pose metadynamics(BPMD), binding free energy calculations, and enzyme activity inhibition analysis are utilized. To maximize efficiency in terms of time and resources, molecules for in vitro activity testing are initially selected from commercially available portions of customized virtual chemical libraries. In vitro studies assessing inhibitor activities have confirmed that the compound EN300-331859shows potential Factor Xa inhibition, with an IC_(50)value of 34.57 μmol·L^(-1). Through in silico molecular docking and BPMD, the most plausible binding pose for the EN300-331859-Factor Xa complex are identified. The estimated binding free energy values correlate well with the results obtained from biological assays. Consequently, EN300-331859 is identified as a novel and effective sub-micromolar inhibitor of Factor Xa.
基金the funding support provided by the Department of Biotechnology(DBT),Government of India(Grant Nos.BT/AB/FG-2 (PH-II)/2009 and BT/PR11705/AGR/02/646/2008)
文摘In marker-assisted breeding for bacterial blight(BB) resistance in rice, three major resistance genes, viz., Xa21, xa13 and xa5, are routinely deployed either singly or in combinations. As efficient and functional markers are yet to be developed for xa13 and xa5, we have developed simple PCR-based functional markers for both the genes. For xa13, we designed a functional PCR-based marker, xa13-prom targeting the In Del polymorphism in the promoter of candidate gene Os8N3 located on chromosome 8 of rice. With respect to xa5, a multiplex-PCR based functional marker system, named xa5 FM, consisting of two sets of primer pairs targeting the 2-bp functional nucleotide polymorphism in the exon II of the gene TFIIA5(candidate for xa5), has been developed. Both xa13-prom and xa5 FM can differentiate the resistant and susceptible alleles for xa13 and xa5, respectively, in a co-dominant fashion. Using these two functional markers along with the already reported functional PCR-based marker for Xa21(p TA248), we designed a single-tube multiplex PCR based assay for simultaneous detection of all the three major resistance genes and demonstrated the utility of the multiplex marker system in a segregating population.
基金Supported by Key Projects of Tianjin Science and Technology Support Plan(12ZCZDSY01100)
文摘The title compound （zifaxaban 2, C20HI6C1N3O4S, Mr = 429.87） was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a = 5.7900（12）, b = 13.086（3）, c = 12.889（3） A, β= 100.86（3）°, V = 959.1（3） ）k3, Z = 2, Dc= 1.489 g/cm3, F（000） = 444,μ= 0.342 mm-l, the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections （I 〉 20（I）. The absolute configuration of the stereogenic center in the title compound was confirmed to be S by single-crystal X-ray diffraction. Four existing intermolecular hydrogen bonds help to stabilize the lattice and the molecule in the lattice to adopt an L-shape conformation. Zifaxaban was slightly more active than rivaroxaban 1 in in vitro assay against human FXa and therefore is promising as a drug candidate.
