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101.
Gérald Larrouy-Maumus Henrieta ?kovierová Rabeb Dhouib Shiva Kumar Angala Sophie Zuberogoitia Ha Pham Anne Drumond Villela Katarina Miku?ová Audrey Noguera Martine Gilleron Lucia Valentínová Jana Korduláková Patrick. J. Brennan Germain Puzo Jér?me Nigou Mary Jackson 《The Journal of biological chemistry》2012,287(47):39933-39941
The biosynthesis of the major cell envelope glycoconjugates of Mycobacterium tuberculosis is topologically split across the plasma membrane, yet nothing is known of the transporters required for the translocation of lipid-linked sugar donors and oligosaccharide intermediates from the cytoplasmic to the periplasmic side of the membrane in mycobacteria. One of the mechanisms used by prokaryotes to translocate lipid-linked phosphate sugars across the plasma membrane relies on translocases that share resemblance with small multidrug resistance transporters. The presence of an small multidrug resistance-like gene, Rv3789, located immediately upstream from dprE1/dprE2 responsible for the formation of decaprenyl-monophosphoryl-β-d-arabinose (DPA) in the genome of M. tuberculosis led us to investigate its potential involvement in the formation of the major arabinosylated glycopolymers, lipoarabinomannan (LAM) and arabinogalactan (AG). Disruption of the ortholog of Rv3789 in Mycobacterium smegmatis resulted in a reduction of the arabinose content of both AG and LAM that accompanied the accumulation of DPA in the mutant cells. Interestingly, AG and LAM synthesis was restored in the mutant not only upon expression of Rv3789 but also upon that of the undecaprenyl phosphate aminoarabinose flippase arnE/F genes from Escherichia coli. A bacterial two-hybrid system further indicated that Rv3789 interacts in vivo with the galactosyltransferase that initiates the elongation of the galactan domain of AG. Biochemical and genetic evidence is thus consistent with Rv3789 belonging to an AG biosynthetic complex, where its role is to reorient DPA to the periplasm, allowing this arabinose donor to then be used in the buildup of the arabinan domains of AG and LAM. 相似文献
102.
J Bussenius CM Blazey N Aay NK Anand A Arcalas T Baik OJ Bowles CA Buhr S Costanzo JK Curtis SC Defina L Dubenko TS Heuer P Huang C Jaeger A Joshi AR Kennedy AI Kim K Lara J Lee J Li JC Lougheed S Ma S Malek JC Manalo JF Martini G McGrath M Nicoll JM Nuss M Pack CJ Peto TH Tsang L Wang SW Womble M Yakes W Zhang KD Rice 《Bioorganic & medicinal chemistry letters》2012,22(17):5396-5404
With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens. 相似文献
103.
R Adepu K Shiva Kumar S Sandra D Rambabu G Rama Krishna C Malla Reddy A Kandale P Misra M Pal 《Bioorganic & medicinal chemistry》2012,20(17):5127-5138
A series of novel N-aryl substituted thieno[2,3-d]pyrimidin-4(3H)-ones were designed and synthesized as potential inhibitors of chorismate mutase. Synthesis of this class of compounds was carried out by using Cu-mediated C-N bond forming reaction between thieno[2,3-d]pyrimidin-4(3H)-ones and aryl boronic acids. The reaction can be performed in an open flask as the conversion was found to be not sensitive to the presence of air or atmospheric moisture. A range of compounds were prepared by using this method and single crystal X-ray diffraction study was performed using a representative compound. In vitro pharmacological data of some of the compounds synthesized along with dose response studies using active molecules are presented. In silico interactions of these molecules with chorismate mutase are also presented. 相似文献
104.
Kumar KS Rambabu D Sandra S Kapavarapu R Krishna GR Basaveswara Rao MV Chatti K Reddy CM Misra P Pal M 《Bioorganic & medicinal chemistry》2012,20(5):1711-1722
A direct and single-step method has been developed for the synthesis of mono and 2,3-disubstituted quinoxalines by using a AlCl(3) induced (hetero)arylation of 2,3-dichloroquinoxaline. Both symmetrical and unsymmetrical 2,3-disubstituted quinoxalines can be prepared conveniently by using this method under appropriate reaction conditions. The reaction proceeds via C-C bond formation and can be utilized for the preparation of a variety of quinoxaline derivatives from readily available starting materials and reagents. The molecular structure of a representative compound was confirmed by single crystal X-ray diffraction study. Some of the compounds synthesized were tested for chorismate mutase inhibitory properties in vitro and one compound showed promising activity representing one of the few examples of chorismate mutase inhibition by a heteroarene based small molecule. 相似文献
105.
Kumar KS Kiran Kumar S Yogi Sreenivas B Gorja DR Kapavarapu R Rambabu D Rama Krishna G Reddy CM Basaveswara Rao MV Parsa KV Pal M 《Bioorganic & medicinal chemistry》2012,20(7):2199-2207
A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl(3)-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC(50) ~0.89 μM) is presented. 相似文献
106.
107.
E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation 总被引:3,自引:0,他引:3 下载免费PDF全文
Zhang K Barragan-Adjemian C Ye L Kotha S Dallas M Lu Y Zhao S Harris M Harris SE Feng JQ Bonewald LF 《Molecular and cellular biology》2006,26(12):4539-4552
Within mineralized bone, osteocytes form dendritic processes that travel through canaliculi to make contact with other osteocytes and cells on the bone surface. This three-dimensional syncytium is thought to be necessary to maintain viability, cell-to-cell communication, and mechanosensation. E11/gp38 is the earliest osteocyte-selective protein to be expressed as the osteoblast differentiates into an osteoid cell or osteocyte, first appearing on the forming dendritic processes of these cells. Bone extracts contain large amounts of E11, but immunostaining only shows its presence in early osteocytes compared to more deeply embedded cells, suggesting epitope masking by mineral. Freshly isolated primary osteoblasts are negative for E11 expression but begin to express this protein in culture, and expression increases with time, suggesting differentiation into the osteocyte phenotype. Osteoblast-like cell lines 2T3 and Oct-1 also show increased expression of E11 with differentiation and mineralization. E11 is highly expressed in MLO-Y4 osteocyte-like cells compared to osteoblast cell lines and primary osteoblasts. Differentiated, mineralized 2T3 cells and MLO-Y4 cells subjected to fluid flow shear stress show an increase in mRNA for E11. MLO-Y4 cells show an increase in dendricity and elongation of dendrites in response to shear stress that is blocked by small interfering RNA specific to E11. In vivo, E11 expression is also increased by a mechanical load, not only in osteocytes near the bone surface but also in osteocytes more deeply embedded in bone. Maximal expression is observed not in regions of maximal strain but in a region of potential bone remodeling, suggesting that dendrite elongation may be occurring during this process. These data suggest that osteocytes may be able to extend their cellular processes after embedment in mineralized matrix and have implications for osteocytic modification of their microenvironment. 相似文献
108.
A combined HPLC-UV/PAD and HPLC-ESI/MS method allowing the fast detection and identification/structural characterisation of lignans of different structural subclasses is described. Twenty-four lignans of different skeletal types were analysed and the combined information derived from their UV and ESI/MS spectra led to the identification of group characteristics that can be used to establish the structure of unknown lignans in plant samples. This method was successfully applied to the identification of lignans in crude extracts of Linum usitatissimum L. and L. bienne Mill. 相似文献
109.
Enhanced single copy integration events in corn via particle bombardment using low quantities of DNA 总被引:3,自引:0,他引:3
Brenda A. Lowe N. Shiva Prakash Melissa Way Michael T. Mann T. Michael Spencer Raghava S. Boddupalli 《Transgenic research》2009,18(6):831-840
Transgene copy number is an important criterion for determining the utility of transgenic events. Single copy integration
events are highly desirable when the objective is to produce marker free plants through segregation or when it is necessary
to introgress different transgenes into commercial cultivars from different transgenic events. In contrast multi-copy events
are advocated by several authors for higher expression of the transgene. Till recently, it was thought that employment of
the particle gun for transformation results in the production of a high proportion of multi-copy events often with complex
integration pattern when compared to Agrobacterium-mediated transformation. However, it has been demonstrated that usage of cassette DNA for bombardment in place of whole plasmids
would result in simple insertion pattern of the transgenes. While investigating the effect of varying the cassette DNA amount
on stable transformation, the frequency of occurrence of low copy events was observed to increase when lower doses of cassette
DNA was employed for bombardment. Large scale experimentation with rigorous statistical analysis performed to verify the above
observations employing Helium gun and the Electric discharge gun for gene delivery confirmed the above observations. Helium
gun experiments involving production of more than 1,600 corn events consistently yielded single copy events at higher frequencies
at lower cassette DNA load (46% at 2.5 ng/shot) as compared to higher cassette DNA load (29% at 25 ng/shot) across 18 independent
experiments. Results were nearly identical with the Electric discharge particle gun device where single copy events were recovered
at frequencies of 54% at 2.5 ng cassettes DNA per shot as compared to 18% at 25 ng cassette DNA per shot. The transformation
frequency declined from 41 to 34% (Helium gun) and from 48 to 31% (Electric discharge gun) with reduction in cassette DNA
quantity from 25 to 2.5 ng per shot. This reduction in the transformation frequency is more than compensated by the savings
in time and effort involved in the production and screening of events if the desired outcome is single copy events. These
results demonstrate the flexibility of the particle gun method for controlling the frequency of production of either low copy
or high copy events by altering the quantity of cassette DNA used for bombardment. The transgene expression levels over generations
in relation to its integration need further investigations. 相似文献
110.
Sharanagouda S. Patil Rajamani Shinduja Kuralayanapalya Puttahonnappa Suresh Sulekha Phukan Sachin Kumar Pinaki Prasad Sengupta Raghavendra G. Amachawadi Ashwin Raut Parimal Roy Asad Syed Najat Marraiki Abdallah M. Elgorban Helal F. Al-Harthi Ali H. Bahkali Chandan Shivamallu Kollur Shiva Prasad 《Saudi Journal of Biological Sciences》2021,28(9):5131-5144
The Indian poultry industry is one of the fast-growing sectors of which duck farming plays an important role. Duck population in India is 33.51 million that is concentrated towards north-east and southern parts of the country who rears mainly for eggs and meat. Duck diseases are of great concern as they badly affect the financial status of the small, landless farmers. Databases such as Google Scholar, PubMed, J gate were used to search articles between 2000 and 2019 that showed the prevalence of viral, bacterial, and parasitic duck diseases. R open source software was used to derive forest plots by statistical analysis. Pooled prevalence estimates of duck diseases worldwide was found to be 20% (95%-CI:15–26). Also, continent-wise analysis of all duck diseases has revealed highest prevalence in North America, followed by Asia, Africa, Europe,Oceania and South America. This prevalence of data would be helpful to the policymakers to develop appropriate intervention strategies to prevent and control diseases in their respective locations. 相似文献