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41.
42.
Goutam Gupta Mukti H. Sarma Ramaswamy H. Sarma 《Journal of biomolecular structure & dynamics》2013,31(6):1457-1472
Abstract Antibiotic netropsin is known to bind specifically to A and T regions in DNA; the mode of binding being non-intercalative. Obviously, H-bonding between the proton donors of netropsin and acceptors N3 of A and 02 of T comes as a strong possibility which might render this specificity. In netropsin there could be 8 proton donors: four terminal amino groups and four internal imino groups. However, methylation of the terminal amino groups does not alter the binding affinity of netropsin to DNA—but the modification of the internal imino groups significantly lowers the binding affinity. Hence, the logical conclusion is that netropsin may specifically interact with A and T through H-bonding and in order to do so, it should approach the helix from the minor groove. The present paper provides experimental data which verify the conclusion mentioned above. Using poly(dA-dT)? poly(dA-dT) as a model system it was observed following a thorough theoretical stereochemical analysis that netropsin could bind to -(T-A-T) sequence of the polymer in the B-form through the minor groove by forming specific B-bonding. Models could be either right or left-handed B-DNA with a mono or dinucleotide repeat. By monitoring the 31P signals of free poly(dA-dT) ? poly(dA-dT) and netropsin-poly(dA-dT)? poly(dA-dT) complex we show that the drug changes the DNA structure from essentially a mononucleotide repeat to that of very dominant dinucleotide repeat; however the base- pairing in the DNA-drug complex remain to be Watson-Crick. Whether H-bonding is the specific mode of interaction was judged by monitoring the imino protons of netropsin in the presence of poly(dA-dT) ? poly(dA-dT). This experiment was conducted in 90% H2O + 10% D2O Using the time-shared long pulse. It was found that exchangeable imino protons of netropsin appear in the drug-DNA complex and disappear upon increasing the D2O content; thus confirming that H-bonding is indeed the specific mode of interaction. From these and several NOE measurements, we propose a structure for poly(dA-dT)? poly(dA-dT(-netropsin complex. In summary, experimental data indicate that netropsin binds to poly(dA-dT)? poly(dA-dT) by forming specific hydrogen bonds and that the binding interaction causes the structure to adopt a Watson-Crick paired dinucleotide repeat motif. The proposed hydrogen bonds can form only if the drug approaches the DNA from the minor groove. Within the NMR time scale the interaction between the ligand and DNA is a fast one. From the NOE experimental data, it appears that poly(dA-dT)? poly(dA-dT) in presence of netropsin exists as an equilibrium mixture of right- and left-handed B-DNA duplexes with a dinucleotide repeat—with a predominance of the left-handed form. The last conclusion is a soft one because it was very difficult to make sure the absence of spin diffusion. In a 400 base pairs long DNA duplex- drug complex (as used in this study), equilibrium between right and left-handed helices can also mean the existence of both helical domains in the same molecule with fast interchange between these domains or/and unhindered motion/propagation of these domains along the helix axis. 相似文献
43.
Sudipta Hazra Subhalakshmi Ghosh Madhushree Das Sarma Smriti Sharma Mousumi Das Prakash Saudagar Vijay Kumar Prajapati Vikash Kumar Dubey Shyam Sundar Banasri Hazra 《Experimental parasitology》2013
World health organization has called for academic research and development of new chemotherapeutic strategies to overcome the emerging resistance and side effects exhibited by the drugs currently used against leishmaniasis. Diospyrin, a bis-naphthoquinone isolated from Diospyros montana Roxb., and its semi-synthetic derivatives, were reported for inhibitory activity against protozoan parasites including Leishmania. Presently, we have investigated the antileishmanial effect of a di-epoxide derivative of diospyrin (D17), both in vitro and in vivo. Further, the safety profile of D17 was established by testing its toxicity against normal macrophage cells (IC50 ∼ 20.7 μM), and also against normal BALB/c mice in vivo. The compound showed enhanced activity (IC50 ∼ 7.2 μM) as compared to diospyrin (IC50 ∼ 12.6 μM) against Leishmania donovani promastigotes. Again, D17 was tested on L. donovani BHU1216 isolated from a sodium stibogluconate-unresponsive patient, and exhibited selective inhibition of the intracellular amastigotes (IC50 ∼ 0.18 μM). Also, treatment of infected BALB/c mice with D17 at 2 mg/kg/day reduced the hepatic parasite load by about 38%. Subsequently, computational docking studies were undertaken on selected enzymes of trypanothione metabolism, viz. trypanothione reductase (TryR) and ornithine decarboxylase (ODC), followed by the enzyme kinetics, where D17 demonstrated non-competitive inhibition of the L. donovani ODC, but could not inhibit TryR. 相似文献
44.
Sweety Mittal Mohini Bhadwal Sudipta Chakraborty H.D. Sarma Sharmila Banerjee M.R.A. Pillai 《Bioorganic & medicinal chemistry letters》2013,23(6):1808-1812
Radiolabeled Arg-Gly-Asp (RGD) peptides are promising agents for non invasive imaging of αvβ3 expression in malignant tumors. The integrin αvβ3 binding affinity and consequent tumor uptake could be improved when a dimeric RGD peptide is used as the targeting moiety instead of a monomer. Towards this, a novel approach was envisaged to synthesize a 99mTc labeled dimeric RGD derivative using a RGD monomer and [99mTcN]+2 intermediate. The dithiocarbamate derivative of cyclic RGD peptide G3-c(RGDfK) (G3 = Gly-Gly-Gly, f = Phe, K = Lys) was synthesized and radiolabeled with [99mTcN]+2 intermediate to form the 99mTcN-[G3-c(RGDfK)]2 complex in high yield (~98%). Biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed good tumor uptake [4.61 ± 0.04% IA/g at 30 min post-injection] with fast clearance of the activity from non-target organs/tissue. Scintigraphic imaging studies showed visible accumulation of activity in the tumor with appreciable target to background ratio. 相似文献
45.
Chunling Lu Qing Liu Aartik Sarma Christopher Fitzpatrick Dennis Falzon Carole D. Mitnick 《PloS one》2013,8(2)
Background
In 2011, World Health Organization revised its recommendation for microbiological monitoring during treatment for multidrug-resistant tuberculosis (MDR-TB) by increasing the frequency of culture examination from quarterly to monthly after culture conversion. Implementing the recommendation requires substantial additional investment in laboratory infrastructure. The objective of this review is to provide cost evidence that is needed for national TB programs to budget for optimal monitoring strategies.Methods and Findings
We conducted the first systematic literature review on unit cost estimates of three monitoring strategies: 1) smear only; 2) culture only; 3) combined smear and culture. 26 peer-reviewed studies were selected by searching 10 databases in English and Chinese for literature published between 1995 and 2012. Cost estimates were converted into 2010 constant USD and international dollars. We assessed the quality of the estimates using a matrix with five essential elements and provided a cost projection for the combined smear and culture tests where the data were available. The 26 studies reported the cost estimates in 16 predominantly high- or middle-income countries from 1993 to 2009. The estimated unit cost for smear, culture, and combined tests ranges from $0.26 to $10.50, $1.63 to $62.01, and $26.73 to $39.57, respectively. The ratio of culture to smear costs varies from 1.35 to 11.98. The wide range of estimates is likely attributable to using different laboratory methods in different regions and years and differing practices in collecting and reporting cost data. Most studies did not report information critical for generalizing their conclusions.Conclusion
The paucity and low quality of unit cost estimates for TB monitoring in resource-poor settings impose technical challenges in predicting the resources needed for strengthening microbiological monitoring. To improve the validity and comparability of the cost data, we strongly advocate the data collection, estimation, and reporting follow protocols proposed by WHO. 相似文献46.
47.
Prantik Sharma Baruah Kishor Deka Lipika Lahkar Bhaskar Sarma S.K. Borthakur Bhaben Tanti 《农业工程》2019,39(1):42-49
Elaeocarpus serratus L., commonly known as ‘rudraksh’ referred in the Ayurveda as a wonderful plant for strengthening body constitutions, has been recognized as a threatened plant of Assam, India. Traditionally, rudraksh beads, its bark and leaves are used to cure various ailments like stress, anxiety, depression, nerve pain, epilepsy, migraine, lack of concentration, asthma, hypertension, arthritis and liver diseases. The population stock of the species has been depleting very fast in its natural habitat due to rapid habitat fragmentation and changing climate altering the structural and functional integrity of the plant. Hence, conservation of E. serratus L. with proper scientific investigation to prevent from extinction in its wild habitat is urgently needed. The present study was emphasized with the specific objectives to study the distribution and population status, predication of suitable sites through ENM, standardization of macropropagation methods and reinforcement/reintroduction into the suitable wild habitat to improve conservation status. In the present investigation E. serratus L. was reported in few locations of Assam and Arunachal Pradesh with population sizes of mean density, frequency of occurrence and abundance in relation to other associated species as 0.333, 13.922 and 2.215 respectively. For improving the conservation status, potential area and habitat for reinforcement was predicted using Maximum Entropy (MaxEnt) distribution modelling algorithm. Subsequently, macropropagation protocol was standardized through seed germination and air-layering; saplings were raised and 1050 saplings were reintroduced to the wild habitats selected on the basis of ecological niche modelling. Survival rate was found significantly high as 68%, suggesting that our approach is effective for changing population status and to conserve the plant. 相似文献
48.
Darshani Priya Sen Sarma Shreya Srivastava Amit K. Baishya Rinku Kumar Deepak 《Phytochemistry Reviews》2022,21(6):1761-1842
Phytochemistry Reviews - Triterpenes are naturally occurring derivatives biosynthesized following the isoprene rule of Ruzicka. The triterpenes have been reported to possess a wide range of... 相似文献
49.
A protocol was developed for high frequency plant regeneration in H. patulum by shoot-tip culture. H. patulum plants were collected from a wild source growing at high altitude in the eastern Himalayas. Multiple buds were initiated from shoot-tips cultured on Murashige and Skoog's medium supplemented with BAP, kinetin. Addition of thiamin HCI, Ca-pantothenate and biotin enhanced multiple shoot formation. Upon transfer to phytohormone free liquid medium following a brief exposure to auxin, root formation occurred from the micro shoots . Rooted plants were hardened and transferred to soil. Regeneration potentiality was found to be constant throughout the year in long term cultures. 相似文献
50.
M.?Sen Sarma H.?Esch J.?TautzEmail author 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2004,190(1):49-53
Honeybees have a dance language by which successful foragers inform nestmates about attractive food patches. The classical concept of dialects in the dance language of honeybees points to two differences in the dances by different species and races, firstly in the flight distance at which the dancers start performing waggle dances instead of round dances, and secondly in the circuit duration of the waggle dance performed for a given flight distance. However, recent findings have indicated that the dance language is influenced and affected by a number of parameters, both genetic and environmental. The current study was carried out to see whether the distance at which dancers change from round dances to waggle dances is statistically different in two different species, Apis mellifera carnica and A. florea and to develop a set of definitions for such comparative studies. Results show that the two species do not differ in the relative proportion of waggle dances and round dances performed at a given distance. Thus, this study points to the need of addressing the dialect question again. 相似文献