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41.
Eight cholesterol based cationic lipids differing in the headgroup have been synthesized based on the ether linkage between the cationic headgroup and the cholesterol backbone. All the lipids formed stable suspensions in water. Transfection efficacies were examined in the absence and presence of serum using their optimized liposomal (lipid:DOPE) formulations. Our results showed that the transfection activities depend on the nature of the headgroup. Lipid bearing 4-N,N′-dimethylaminopyridine (DMAP) as headgroup showed the maximum transfection efficacy in the presence of serum. Importantly, the optimized formulation for this cationic lipid does not require DOPE, which is being used by most commercially available formulations. Cytotoxicity studies showed that the introduction of the positive charge decreases the cell viability of the cationic lipid formulations. Gel electrophoresis and Ethidium bromide exclusion assay revealed the different DNA binding abilities of formulations depending upon the headgroup of the cholesteryl lipid. 相似文献
42.
Neil A. Koorbanally Neil R. Crouch Avinash Harilal Bavani Pillay Dulcie A. Mulholland 《Biochemical Systematics and Ecology》2006
We report on the first phytochemical investigation of a member of the African genus Resnova (Hyacinthoideae: Hyacinthaceae). From the dichloromethane extract of the bulbs of both Resnova humifusa and Eucomis montana (Hyacinthoideae: Hyacinthaceae) a novel 3-benzyl-4-chromanone homoisoflavonoid, 5,6-dimethoxy-7-hydroxy-3-(4′-hydroxybenzyl)-4-chromanone, was isolated. A further 11 known homoisoflavonoids were also identified, the 12 in total presenting a clear biosynthetic sequence. Eight of the 12 compounds found were common to both species. 相似文献
43.
Marc Kschonsak Lionel Rougé Christopher P. Arthur Ho Hoangdung Nidhi Patel Ingrid Kim Matthew C. Johnson Edward Kraft Alexis L. Rohou Avinash Gill Nadia Martinez-Martin Jian Payandeh Claudio Ciferri 《Cell》2021,184(5):1232-1244.e16
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44.
Avinash S. Punekar Tyson R. Shepherd Josefine Liljeruhm Anthony C. Forster Maria Selmer 《Nucleic acids research》2012,40(20):10507-10520
RlmM (YgdE) catalyzes the S-adenosyl methionine (AdoMet)-dependent 2′O methylation of C2498 in 23S ribosomal RNA (rRNA) of Escherichia coli. Previous experiments have shown that RlmM is active on 23S rRNA from an RlmM knockout strain but not on mature 50S subunits from the same strain. Here, we demonstrate RlmM methyltransferase (MTase) activity on in vitro transcribed 23S rRNA and its domain V. We have solved crystal structures of E. coli RlmM at 1.9 Å resolution and of an RlmM–AdoMet complex at 2.6 Å resolution. RlmM consists of an N-terminal THUMP domain and a C-terminal catalytic Rossmann-like fold MTase domain in a novel arrangement. The catalytic domain of RlmM is closely related to YiiB, TlyA and fibrillarins, with the second K of the catalytic tetrad KDKE shifted by two residues at the C-terminal end of a beta strand compared with most 2′O MTases. The AdoMet-binding site is open and shallow, suggesting that RNA substrate binding may be required to form a conformation needed for catalysis. A continuous surface of conserved positive charge indicates that RlmM uses one side of the two domains and the inter-domain linker to recognize its RNA substrate. 相似文献
45.
46.
Venkat R. Gadhachanda Kyle J. Eastman Qiuping Wang Avinash S. Phadke Dharaben Patel Wengang Yang Christopher W. Marlor Milind Deshpande Mingjun Huang Jason A. Wiles 《Bioorganic & medicinal chemistry letters》2018,28(21):3463-3471
An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1′-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat. 相似文献
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48.
Bernard J Premraj Swaminathan Raja Neel S Bhavesh Ke Shi Ramakrishna V Hosur Muttaiya Sundaralingam Narayanarao Yathindra 《European journal of biochemistry》2004,271(14):2956-2966
The NMR structure of 2',5' d(GGGGCCCC) was determined to gain insights into the structural differences between 2',5'- and 3',5'-linked DNA duplexes that may be relevant in elucidating nature's choice of sugar-phosphate links to encode genetic information. The oligomer assumes a duplex with extended nucleotide repeats formed out of mostly N-type sugar puckers. With the exception of the 5'-terminal guanine that assumes the syn glycosyl conformation, all other bases prefer the anti glycosyl conformation. Base pairs in the duplex exhibit slide (-1.96 A) and intermediate values for X-displacement (-3.23 A), as in ADNA, while their inclination to the helical axis is not prominent. Major and minor grooves display features intermediate to A and BDNA. The duplex structure of iso d(GGGGCCCC) may therefore be best characterized as a hybrid of A and BDNA. Importantly, the results confirm that even 3' deoxy 2',5' DNA supports duplex formation only in the presence of distinct slide (>or=-1.6 A) and X-displacement (>or=-2.5 A) for base pairs, and hence does not favor an ideal BDNA topology characterized by their near-zero values. Such restrictions on base pair movements in 2',5' DNA, which are clearly absent in 3',5' DNA, are expected to impose constraints on its ability for deformability of the kind observed in DNA during its compaction and interaction with proteins. It is therefore conceivable that selection pressure relating to the optimization of topological features might have been a factor in the rejection of 2',5' links in preference to 3',5' links. 相似文献
49.
Mahendra Rai Avinash P. Ingle Swapnil Gaikwad Felipe Hering Padovani Monica Alves 《Critical reviews in biotechnology》2016,36(5):777-787
Nanotechnology is the creation and use of materials and devices on the same scale as molecules and intracellular structures, typically less than 100?nm in size. It is an emerging science and has made its way into pharmaceuticals to significantly improve the delivery and efficacy of drugs in a number of therapeutic areas, due to development of various nanoparticle-based products. In recent years, there has been increasing evidence that nanotechnology can help to overcome many of the ocular diseases and hence researchers are keenly interested in this science. Nanomedicines offer promise as viable alternatives to conventional drops, gels or ointments to improve drug delivery to the eye. Because of their small size, they are well tolerated, thus preventing washout, increase bioavailability and also help in specific drug delivery. This review describes the application of nanotechnology in the control of human diseases with special emphasis on various eye and ocular surfaces diseases. 相似文献
50.
Lung surfactant secretion in alveolar type II cells occurs following lamellar body fusion with plasma membrane. Annexin A7 is a Ca2+-dependent membrane-binding protein that is postulated to promote membrane fusion during exocytosis in some cell types including type II cells. Since annexin A7 preferably binds to lamellar body membranes, we postulated that specific lipids could modify the mode of annexin A7 interaction with membranes and its membrane fusion activity. Initial studies with phospholipid vesicles containing phosphatidylserine and other lipids showed that certain lipids affected protein interaction with vesicle membranes as determined by change in protein tryptophan fluorescence, protein interaction with trans membranes, and by protein sensitivity to limited proteolysis. The presence of signaling lipids, diacylglycerol or phosphatidylinositol-4,5-bisphosphate, as minor components also modified the lipid vesicle effect on these characteristics and membrane fusion activity of annexin A7. In vitro incubation of lamellar bodies with diacylglycerol or phosphatidylinositol-4,5-bisphosphate caused their enrichment with either lipid, and increased the annexin A7 and Ca2+-mediated fusion of lamellar bodies. Treatment of isolated lung lamellar bodies with phosphatidylinositol- or phosphatidylcholine phospholipase C to increase diacylglycerol, without or with preincubation with phosphatidylinositol-4,5-bisphosphate, augmented the fusion activity of annexin A7. Thus, increased diacylglycerol in lamellar bodies following cell stimulation with secretagogues may enhance membrane fusion activity of annexin A7. 相似文献