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31.
Raman Spectroscopy and Fluorescence Photon Migration for Breast Cancer Diagnosis and Imaging 总被引:3,自引:0,他引:3
Ramasamy Manoharan Karen Shafer Lev Perelman Jun Wu Kun Chen Geurt Deinum Maryann Fitzmaurice Jonathan Myles Joseph Crowe Ramachandra R. Dasarl Michael S. Feld 《Photochemistry and photobiology》1998,67(1):15-22
We are developing optical methods based on near infra-red Raman spectroscopy and fluorescence photon migration for diagnosis and localization of breast cancer. We demonstrate the ability of Raman spectroscopy to classify accurately normal, benign and malignant breast tissues, an important step in developing Raman spectroscopic needle probes as a tool for improving the accuracy of needle biopsy. We also show that photon migration imaging can be used to localize accurately small fluorescent objects imbedded in a thick turbid medium with realistic optical properties, thus demonstrating the potential of this technique for optical imaging. 相似文献
32.
[structure: see text] Oligonucleotides with novel modifications, 2'-O-[2-(amino)-2-oxoethyl] (2'-O-NAc), 2'-O-[2-(methylamino)-2-oxoethyl] (2'-O-NMAc), 2'-O-[2-(dimethylamino)-2-oxoethyl] (2'-O-DMAc), and 2'-O-[2-[[2-(dimethylamino)ethyl]amino]-2-oxoethyl] (2'-O-DMAEAc), have been synthesized. These modified oligonucleotides exhibit high binding affinity to complementary RNA (and not to DNA) and considerably enhance the nuclease stability of oligonucleotides with t(1/2) > 24 h. 相似文献
33.
Phosphoramidite coupling to oligonucleotides bearing unprotected internucleosidic phosphate moieties
The coupling of 2-cyanoethyl thymidine phosphoramidite to solid-support-bound, phosphate-unprotected oligothymidylates and their phosphorothioate analogues was studied. The yield of the coupling reaction depended on the pK(BH)()+ values of protonated nitrogen bases that served as counterions to the phosphodiester functions of oligonucleotides. To maximize the coupling efficiency, the oligonucleotides were detritylated and washed with a mixture of 0.1 M DMAP and 0.1 M 1H-tetrazole, which resulted in a 98+% coupling efficiency. The utility of the results was demonstrated in the preparation of oligonucleotides with a mixed backbone that required the successive use of H-phosphonate and phosphoramidite methods of synthesis. Using this approach, 20-mer antisense oligonucleotides containing 2'-O-(2-methoxyethyl) ribonucleoside residues and phosphorothioate and phosphoramidate internucleosidic linkages were synthesized in high yield. 相似文献
34.
J.B. Goodenough A. Hamnett B.J. Kennedy R. Manoharan S.A. Weeks 《Journal of Electroanalytical Chemistry》1988,240(1-2)
A novel Pt + Ru electrode material is shown to be highly active for the direct electro-oxidation of methanol in H2SO4 solutions and to show very little tendency to poison. X-ray photoelectron spectroscopy of this material before use as an anode showed that the ruthenium is oxidised and that there is an important surface concentration of oxidised platinum. After prolonged use as a methanol-oxidation anode, the concentration of oxidised platinum is somewhat increased and there is no evidence for any Pt-CO or Pt2 = CO species; rather adsorbed formate is present. These data are consistent with Ru acting as a promoter of active surface oxygen. Dispersion of the Pt and Ru on a pure carbon support gives a much greater performance per gram of precious metal; however, the initial increase in overpotential is greater by over 100 mV. The differences in the catalytic behaviour of these two materials is discussed, and the importance of competing reactions is considered. 相似文献
35.
Pattanayek R Sethaphong L Pan C Prhavc M Prakash TP Manoharan M Egli M 《Journal of the American Chemical Society》2004,126(46):15006-15007
Chemical modification of nucleic acids at the 2'-position of ribose has generated antisense oligonucleotides (AONs) with a range of desirable properties. Electron-withdrawing substituents such as 2'-O-[2-(methoxy)ethyl] (MOE) confer enhanced RNA affinity relative to that of DNA by conformationally preorganizing an AON for pairing with the RNA target and by improving backbone hydration. 2'-Substitution of the ribose has also been shown to increase nuclease resistance and cellular uptake via changes in lipophilicity. Interestingly, incorporation of either 2'-O-[2-(methylamino)-2-oxoethyl]- (NMA) or 2'-O-(N-methylcarbamate)-modified (NMC) residues into AONs has divergent effects on RNA affinity. Incorporation of 2'-O-NMA-T considerably improves RNA affinity while incorporation of 2'-O-NMC-T drastically reduces RNA affinity. Crystal structures at high resolution of A-form DNA duplexes containing either 2'-O-NMA-T or 2'-O-NMC-T shed light on the structural origins of the surprisingly large difference in stability given the relatively minor difference in chemistry between NMA and NMC. NMA substituents adopt an extended conformation and use either their carbonyl oxygen or amino nitrogen to trap water molecules between phosphate group and sugar. The conformational properties of NMA and the observed hydration patterns are reminiscent of those found in the structures of 2'-O-MOE-modified RNA. Conversely, the carbonyl oxygen of NMC and O2 of T are in close contact, providing evidence that an unfavorable electrostatic interaction and the absence of a stable water structure are the main reasons for the loss in thermodynamic stability as a result of incorporation of 2'-O-NMC-modified residues. 相似文献
36.
Prabu Manoharan R. S. K. Vijayan Nanda Ghoshal 《Journal of computer-aided molecular design》2010,24(10):843-864
The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment
based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to
rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated
on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor
in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values.
A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn
used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered
in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR)
method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability
algorithm to identify the optimal level of independent variables (X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated
using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion,
the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate
some prospective novel, potent and selective BACE1 inhibitors. 相似文献
37.
Fast anionic oxy-Cope rearrangements of 1,5-hexadiyn-3,4-olates can be incorporated into cascade transformations which rapidly assemble densely functionalized cyclobutenes or cyclopentenones via a common bis-allenic intermediate. The competition between fragmentation, 4π-electrocyclic closure, and aldol condensation can be efficiently controlled by the nature of the acetylenic substituents. The rearrangement of bis-alkynes with two hydroxyl substituents opens a conceptually interesting entry in the chemistry of ε-dicarbonyl compounds and suggests a new approach to analogues of rocaglamide/aglafolin. 相似文献
38.
[structure: see text] Oligonucleotides with a novel, 2'-O-[2-[2-(N,N-dimethylamino)ethoxy]ethyl] (2'-O-DMAEOE) modification have been synthesized. This modification, a cationic analogue of the 2'-O-(2-methoxyethyl) (2'-O-MOE) modification, exhibits high binding affinity to target RNA (but not to DNA) and exceptional resistance to nuclease degradation. Analysis of the crystal structure of a self-complementary oligonucleotide containing a single 2'-O-DMAEOE modification explains the importance of charge factors and gauche effects on the observed antisense properties. 2'-O-DMAEOE modified oligonucleotides are ideal candidates for antisense drugs. 相似文献
39.
Palanivel Manoharan 《Proceedings of the American Mathematical Society》1998,126(4):1205-1210
The space of smooth sections of a bundle over a compact smooth manifold can be equipped with a manifold structure, called an -manifold, where represents the Fréchet algebra of real valued smooth functions on . We prove that the -manifold structure characterizes the spaces of sections of bundles over and its open subspaces. We also describe the -maps between -manifolds.
40.