排序方式: 共有24条查询结果,搜索用时 15 毫秒
1.
Vaisburg A Bernstein N Frechette S Allan M Abou-Khalil E Leit S Moradei O Bouchain G Wang J Woo SH Fournel M Yan PT Trachy-Bourget MC Kalita A Beaulieu C Li Z MacLeod AR Besterman JM Delorme D 《Bioorganic & medicinal chemistry letters》2004,14(1):283-287
A variety of omega-substituted alkanoic acid (2-amino-phenyl)-amides were designed and synthesized. These compounds were shown to inhibit recombinant human histone deacetylases (HDACs) with IC(50) values in the low micromolar range and induce hyperacetylation of histones in whole cells. They induced expression of p21WAF1/Cip1 and caused cell-cycle arrest in human cancer cells. Compounds in this class showed efficacy in human tumor xenograft models. 相似文献
2.
Morgan A Bishop Arkadii G D' Yachkov Anthony J Macula Thomas E Renz Vyacheslav V Rykov 《Journal of computational biology》2007,14(8):1088-1104
DNA nanotechnology often requires collections of oligonucleotides called "DNA free energy gap codes" that do not produce erroneous crosshybridizations in a competitive muliplexing environment. This paper addresses the question of how to design these codes to accomplish a desired amount of work within an acceptable error rate. Using a statistical thermodynamic and probabilistic model of DNA code fidelity and mathematical random coding theory methods, theoretical lower bounds on the size of DNA codes are given. More importantly, DNA code design parameters (e.g., strand number, strand length and sequence composition) needed to achieve experimental goals are identified. 相似文献
3.
Bobko AA Sergeeva SV Bagryanskaya EG Markel AL Khramtsov VV Reznikov VA Kolosova NG 《Biochemical and biophysical research communications》2005,330(2):367-370
Recently we demonstrated the principal possibility of application of 19F NMR spin-trapping technique for in vivo *NO detection [Free Radic. Biol. Med. 36 (2004) 248]. In the present study, we employed this method to elucidate the significance of *NO availability in animal models of hypertension. In vivo *NO-induced conversion of the hydroxylamine of the fluorinated nitronyl nitroxide (HNN) to the hydroxylamine of the iminonitroxide (HIN) in hypertensive ISIAH and OXYS rat strains and normotensive Wistar rat strain was measured. Significantly lower HIN/HNN ratios were measured in the blood of the hypertensive rats. The NMR data were found to positively correlate with the levels of nitrite/nitrate evaluated by Griess method and negatively correlate with the blood pressure. In comparison with other traditionally used methods 19F NMR spectroscopy allows in vivo evaluation of *NO production and provides the basis for in vivo *NO imaging. 相似文献
4.
Arkadii V. Tarasevych Thomas Vives Valeriy N. Snytnikov Jean-Claude Guillemin 《Origins of life and evolution of the biosphere》2017,47(3):371-379
The heating above 400 °C of serine, cysteine, selenocysteine and threonine leads to a complete decomposition of the amino acids and to the formation in low yields of alanine for the three formers and of 2-aminobutyric acid for the latter. At higher temperature, this amino acid is observed only when sublimable α-alkyl-α-amino acids are present, and with an enantiomeric excess dependent on several parameters. Enantiopure or enantioenriched Ser, Cys, Sel or Thr is not able to transmit its enantiomeric excess to the amino acid formed during its decomposition. The presence during the sublimation-decomposition of enantioenriched valine or isoleucine leads to the enantioenrichment of all sublimable amino acids independently of the presence of many decomposition products coming from the unstable derivative. All these studies give information on a potentially prebiotic key-reaction of abiotic transformations between α-amino acids and their evolution to homochirality. 相似文献
5.
Oscar M. Saavedra Ljubomir Isakovic David B. Llewellyn Lijie Zhan Naomy Bernstein Stephen Claridge Franck Raeppel Arkadii Vaisburg Nadine Elowe Andrea J. Petschner Jubrail Rahil Norman Beaulieu A. Robert MacLeod Daniel Delorme Jeffrey M. Besterman Amal Wahhab 《Bioorganic & medicinal chemistry letters》2009,19(10):2747-2751
The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH– without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N6-amino moiety favors the inhibition of DNMT3b2 enzyme. 相似文献
6.
Ljubomir Isakovic Oscar M. Saavedra David B. Llewellyn Stephen Claridge Lijie Zhan Naomy Bernstein Arkadii Vaisburg Nadine Elowe Andrea J. Petschner Jubrail Rahil Norman Beaulieu France Gauthier A. Robert MacLeod Daniel Delorme Jeffrey M. Besterman Amal Wahhab 《Bioorganic & medicinal chemistry letters》2009,19(10):2742-2746
Potent SAH analogues with constrained homocysteine units have been designed and synthesized as inhibitors of human DNMT enzymes. The five membered (2S,4S)-4-mercaptopyrrolidine-2-carboxylic acid, in 1a, was a good replacement for homocysteine, while the corresponding six-member counterpart was less active. Further optimization of 1a, changed the selectivity profile of these inhibitors. A Chloro substituent at the 2-position of 1a, compound 1d, retained potency against DNMT1, while N6 alkylation, compound 7a, conserved DNMT3b2 activity. The concomitant substitutions of 1a at both 2- and N6 positions reduced activity against both enzymes. 相似文献
7.
Dmitry I. Osmakov Sergey A. Kozlov Yaroslav A. Andreev Sergey G. Koshelev Nadezhda P. Sanamyan Karen E. Sanamyan Igor A. Dyachenko Dmitry A. Bondarenko Arkadii N. Murashev Konstantin S. Mineev Alexander S. Arseniev Eugene V. Grishin 《The Journal of biological chemistry》2013,288(32):23116-23127
Three novel peptides were isolated from the venom of the sea anemone Urticina grebelnyi. All of them are 29 amino acid peptides cross-linked by two disulfide bridges, with a primary structure similar to other sea anemone peptides belonging to structural group 9a. The structure of the gene encoding the shared precursor protein of the identified peptides was determined. One peptide, π-AnmTX Ugr 9a-1 (short name Ugr 9-1), produced a reversible inhibition effect on both the transient and the sustained current of human ASIC3 channels expressed in Xenopus laevis oocytes. It completely blocked the transient component (IC50 10 ± 0.6 μm) and partially (48 ± 2%) inhibited the amplitude of the sustained component (IC50 1.44 ± 0.19 μm). Using in vivo tests in mice, Ugr 9-1 significantly reversed inflammatory and acid-induced pain. The other two novel peptides, AnmTX Ugr 9a-2 (Ugr 9-2) and AnmTX Ugr 9a-3 (Ugr 9-3), did not inhibit the ASIC3 current. NMR spectroscopy revealed that Ugr 9-1 has an uncommon spatial structure, stabilized by two S-S bridges, with three classical β-turns and twisted β-hairpin without interstrand disulfide bonds. This is a novel peptide spatial structure that we propose to name boundless β-hairpin. 相似文献
8.
Arkadii V. Tarasevych Alexander E. Sorochinsky Valery P. Kukhar Jean-Claude Guillemin 《Origins of life and evolution of the biosphere》2013,43(2):129-135
Deracemization of a 50/50 mixture of enantiomers of aliphatic amino acids (Ala, Leu, Pro, Val) can be achieved by a simple sublimation of a pre-solubilized solid mixture of the racemates with a huge amount of a less-volatile optically active amino acid (Asn, Asp, Glu, Ser, Thr). The choice of chirality correlates with the handedness of the enantiopure amino acids—Asn, Asp, Glu, Ser, and Thr. The deracemization, enantioenrichment and enantiodepletion observed in these experiments clearly demonstrate the preferential homochiral interactions and a tendency of natural amino acids to homochiral self-organization. These data may contribute toward an ultimate understanding of the pathways by which prebiological homochirality might have emerged. 相似文献
9.
Fréchette S Leit S Woo SH Lapointe G Jeannotte G Moradei O Paquin I Bouchain G Raeppel S Gaudette F Zhou N Vaisburg A Fournel M Yan PT Trachy-Bourget MC Kalita A Robert MF Lu A Rahil J Robert Macleod A Besterman JM Li Z Delorme D 《Bioorganic & medicinal chemistry letters》2008,18(4):1502-1506
The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC(50) values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21(WAF1/Cip1), and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo. 相似文献
10.
Stéphane Raeppel Stephen Claridge Oscar Saavedra Frédéric Gaudette Lijie Zhan Michael Mannion Nancy Zhou Franck Raeppel Marie-Claude Granger Ljubomir Isakovic Robert Déziel Hannah Nguyen Normand Beaulieu Carole Beaulieu Isabelle Dupont Marie-France Robert Sylvain Lefebvre Marja Dubay Jubrail Rahil James Wang Arkadii Vaisburg 《Bioorganic & medicinal chemistry letters》2009,19(5):1323-1328
A series of N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases was designed and synthesized. The compounds were potent against these two enzymes with IC50 values in the low nanomolar range in vitro, possessed favorable pharmacokinetic profiles and showed high efficacy in vivo in several human tumor xenograft models in mice. 相似文献