Abstract:
:In this study, a number of 2',4'-BNA- and 2',4'-BNA(NC)-modified siRNAs were designed and synthesized. Their thermal stability, nuclease resistance and gene silencing properties against cultured mammalian cells were evaluated and compared with those of natural siRNAs. The 2',4'-BNA- and 2',4'-BNA(NC)-modified siRNAs (named siBNA and siBNA(NC), respectively) showed very high T(m) values, were remarkably stable in serum sample and showed promising RNAi properties equal to those exhibited by natural siRNAs. Thermally stable siBNAs composed of slightly modified sense and antisense strands were capable of suppressing gene expression equal to that of natural siRNA. A number of modifications on the sense strand by 2',4'-BNA or 2',4'-BNA(NC), either consecutively or separated by natural RNA nucleotides, is tolerable in RNAi machinery. Modifications at the Argonauate (Ago2) cleavage site of the sense strand (9-11th positions from the 5'-end of the sense strand) produced variable results depending on siRNA composition. Mostly, modification at the 10th position diminished siRNA activity. In moderately modified siRNAs, modification at the 11th position displayed usual RNAi activity, while modification at the 9th position showed variable results depending on siRNA composition.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Abdur Rahman SM,Sato H,Tsuda N,Haitani S,Narukawa K,Imanishi T,Obika Sdoi
10.1016/j.bmc.2010.03.076subject
Has Abstractpub_date
2010-05-15 00:00:00pages
3474-80issue
10eissn
0968-0896issn
1464-3391pii
S0968-0896(10)00290-7journal_volume
18pub_type
杂志文章abstract::A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.06.022
更新日期:2007-09-15 00:00:00
abstract::The peptides DRPVPY and MDWNMHAA, which were identified as mimics of the cell-surface polysaccharides of Streptococcus Group A and Shigella flexneri Y, respectively, were used in this study to develop experimental vaccines directed against these two bacteria. Both oligopeptides were synthesized employing the Fmoc soli...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.03.075
更新日期:2004-07-01 00:00:00
abstract::The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.04.006
更新日期:2004-06-15 00:00:00
abstract::To develop nonprostanoid prostacyclin receptor agonists with a high degree of metabolic resistance and an extended duration of action, a novel series of diphenylpyrazine derivatives was synthesized and evaluated for their inhibition of ADP-induced human platelet aggregation. Structure-activity relationship studies on ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.08.010
更新日期:2007-11-01 00:00:00
abstract::Aspartate-β-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the aspartate metabolic pathway which leads to the biosynthesis of several essential amino acids and some important metabolites. This pathway is crucial for many metabolic processes in plants and microbes like bacteria and fungi, but is a...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2015.09.017
更新日期:2015-10-15 00:00:00
abstract::Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00128-0
更新日期:2000-08-01 00:00:00
abstract::The serotonin receptor 6 (5-HT(6)) is implicated in the pathophysiology of cognitive diseases, schizophrenia, anxiety and obesity and in vivo studies of this receptor would be of value for studying the pathophysiology of these disorders. Therefore, N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzen...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.06.090
更新日期:2011-09-01 00:00:00
abstract::A series of novel benzimidazole derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the HepG2.2.15 cell line. The preliminary SAR was discussed. Compound 12a, with IC50<0.41 microM and SI>81.2, was the most promising compound and selected as the benchmark comp...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.05.076
更新日期:2010-07-15 00:00:00
abstract::An efficient synthesis of a library of 5-amino-thiazolo[4,5-d]pyrimidines is reported. Regioselective displacements of chlorines, as well as regioselective diazotation reactions are described, which allow the introduction of structural diversity on the scaffold by consecutive reactions. Screening of this focused libra...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.10.027
更新日期:2011-01-01 00:00:00
abstract::Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contribu...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.12.019
更新日期:2012-02-01 00:00:00
abstract::Structural features and hydrogen-bond interactions of dinotefuran (DIN), imidacoloprid (IMI) and acetamiprid (ACE) have been investigated experimentally through analyses of new crystal structures and observations in structural databases, as well as by Density Functional Theory quantum chemical calculations. Several co...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.10.019
更新日期:2011-12-15 00:00:00
abstract::A new series of synthetic flavones, thioflavones, and flavanones has been synthesized and evaluated as potential inhibitors of monoamine oxidase isoforms (MAO-A and -B). The most active series is the flavanone one with higher selective inhibitory activity against MAO-B. Some of these flavanones (mainly the most effect...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.12.029
更新日期:2010-02-01 00:00:00
abstract::We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1-4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1-4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibo...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.01.011
更新日期:2018-03-01 00:00:00
abstract::We have surveyed the utility of Beckmann rearrangement for the conversion of indanones into carbostyrils. Initial attempts at the conversion of 6-methoxy indanone oxime under classical conditions resulted in the formation of the two unusual products: 2-sulfonyloxyindanone and the dimeric product. This unusual rearrang...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(03)00116-0
更新日期:2003-05-15 00:00:00
abstract::Bioactive compounds present in grapefruit juice are known to increase the bioavailability of certain medications by acting as potent CYP 3A4 inhibitors. An efficient technique has been developed for isolation and purification of three furocoumarins. The isolated compounds have been tested for the inhibition of human C...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.11.039
更新日期:2006-04-15 00:00:00
abstract::Novel heterodimer analogues of melatonin were synthesized, when agomelatine (1) and various aryl units are linked via a linear alkyl chain through the methoxy group. The compounds were tested for their actions at melatonin receptors. Several of these ligands are MT(1)-selective with nanomolar or subnanomolar affinity....
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.04.008
更新日期:2010-05-15 00:00:00
abstract::Selenium-incorporated fucoses (seleno-fucoses) differing in the position of the seleno-substituent were synthesized and applied to the X-ray structural determination of a carbohydrate-lectin complex using single/multi-wavelength anomalous dispersion (SAD/MAD) phasing. The hydroxyl groups at the C-1, -2, -3 and -4 posi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.12.021
更新日期:2017-02-01 00:00:00
abstract::The synthesis of a neoglycopeptide building block is described. The key step is a cycloaddition where the chemistry is orthogonal to standard glycosyl transfer methodology. Also described is some exploratory chemistry of the building block. ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(03)00182-2
更新日期:2003-07-03 00:00:00
abstract::A series of 16 1-phenyl-1H-1,2,3-triazoles with substituents at both the 4- and 5-positions of the triazole ring were synthesized, and a total of 49 compounds, including previously reported 4- or 5-monosubstituted analogues, were examined for their ability to inhibit the specific binding of [(3)H]4'-ethynyl-4-n-propyl...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.05.039
更新日期:2007-08-01 00:00:00
abstract::The permeability of dipeptide derivatives containing tryptophans and indole derivatives through Caco-2 cells was used as an in vitro intestinal absorption model in order to clarify structural factors which influence their intestinal epithelial permeation and metabolism. Most peptide derivatives were hydrolysed not onl...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2003.10.001
更新日期:2004-01-02 00:00:00
abstract::Caffeic acid esters, one of the components of propolis, are known to show a variety of biological effects such as anti-tumor, anti-oxidant, and anti-inflammatory activities. Although, the anti-inflammatory activities of caffeic acid esters have been studied by analyzing their structure, the detailed mechanisms of thei...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.07.006
更新日期:2008-08-15 00:00:00
abstract::Novel 5-benzyl and 5-benzylidene-thiazolidine-2,4-diones carrying 2,3-dihydrobenzo[1,4]dioxin pharmacophore were synthesized and their glycogen phosphorylase inhibitor activity was also studied. ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.03.084
更新日期:2007-06-15 00:00:00
abstract::The crystal structure of ABT-378 (lopinavir), bound to the active site of HIV-1 protease is described. A comparison with crystal structures of ritonavir, A-78791, and BILA-2450 shows some analogous features with previous reported compounds. A cyclic urea unit in the P(2) position of ABT-378 is novel and makes two bide...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00051-2
更新日期:2002-08-01 00:00:00
abstract::Novel chemical entities were prepared via Suzuki and S(N) reaction as AC-ring substrate mimetics of CYP17. The synthesised compounds 1-31 were tested for activity using human CYP17 expressed in Escherichia coli. Promising compounds were tested for selectivity against hepatic CYP enzymes (3A4, 2D6, 1A2, 2C9, 2C19, 2B6)...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.10.094
更新日期:2008-02-15 00:00:00
abstract::A facile synthesis of dl-6,10,14-trimethylpentadecan-2-ol (1) a pheromone component of rice moth, Corcyra cephalonica Stainton and 5,9,13-trimethyltetradecanoic acid (2) a component of marine sponge, Cinachyrella alloclada Uliczka, using a common, intermediate, hexahydrofarnesol is accomplished. The salient features f...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)82149-5
更新日期:1993-12-01 00:00:00
abstract::Seven new nitrogen heterocycle porphyrins, 5,10,15,20-tetra[4-(N-pyrrolidinyl)phenyl]porphine (TBPPH(2)), 5,10,15,20-tetra[4-(4'-ethylpiperazinyl)phenyl]porphine (TEPPH(2)), 5,10,15,20-tetra [4-(4'-butylpiperazinyl)phenyl]porphine (TUPPH(2)), 5,10,15,20-tetra[4-(4'-heptylpiperazinyl) phenyl]porphine (THPPH(2)), 5-[4-(...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(03)00027-0
更新日期:2003-04-17 00:00:00
abstract::Functionalized benzylidene-indolin-2-ones are widely associated with antiproliferative activity. The scaffold is not normally associated with chemoprevention in spite of the presence of a nitrogen-linked Michael acceptor moiety that may predispose members to induction of NQO1, a widely used biomarker of chemopreventiv...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.12.052
更新日期:2009-03-01 00:00:00
abstract::The present report describes the synthesis and anticancer evaluation of certain 11-substituted 6H-indolo[2,3-b]quinolines and their methylated derivatives. These 6H-indolo[2,3-b]quinoline derivatives 11-13 were prepared from the commercially available 1,4-dihydroxyquinoline through alkylation, chlorination, nucleophil...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.09.025
更新日期:2004-12-15 00:00:00
abstract::It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both i.v. and p.o. administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1, generated by human liver microsomes as 20a, a hydroxylated compound at the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(03)00454-1
更新日期:2003-10-01 00:00:00
abstract::4-Oxalocrotonate tautomerase (4-OT) catalyzes the isomerization of 4-oxalocrotonate, 1, to 2-oxo-3E-hexenedioate, 3, using a general acid/base mechanism that involves a conserved N-terminal proline residue. The P1A and P1G mutants have been shown to catalyze this isomerization but at reduced rates. Analysis of these m...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00385-1
更新日期:2002-12-01 00:00:00