共查询到20条相似文献,搜索用时 31 毫秒
1.
T. Santhosh Kumar Jesper Wengel Patrick J. Hrdlicka 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1407-1409
Oligodeoxyribonucleotides (ONs) containing two incorporations of 2 ′-N-(pyren-1-yl)acetyl-2 ′-amino-α-L-LNA monomer Y are sensitive probes for detection of single nucleotide polymorphisms (SNP) in DNA. In addition, the ability of ONs containing pyrene-functionalized 2 ′-amino-α-L-LNA monomers ( W-Z ) to stabilize duplexes with an abasic site is demonstrated. 相似文献
2.
P. V. Balaji W. Saenger V. S.R. Rao 《Journal of biomolecular structure & dynamics》2013,31(5):959-969
Abstract The modes of binding of adenosine 2′-monophosphate (2′-AMP) to the enzyme ribonuclease (RNase) T1 were determined by computer modelling studies. The phosphate moiety of 2′-AMP binds at the primary phosphate binding site. However, adenine can occupy two distinct sites - (1) The primary base binding site where the guanine of 2′-GMP binds and (2) The subsite close to the N1 subsite for the base on the 3′-side of guanine in a guanyl dinucleotide. The minimum energy conformers corresponding to the two modes of binding of 2′-AMP to RNase T1 were found to be of nearly the same energy implying that in solution 2′-AMP binds to the enzyme in both modes. The conformation of the inhibitor and the predicted hydrogen bonding scheme for the RNase T1 - 2′-AMP complex in the second binding mode (S) agrees well with the reported x-ray crystallographic study. The existence of the first mode of binding explains the experimental observations that RNase T1 catalyses the hydrolysis of phosphodiester bonds adjacent to adenosine at high enzyme concentrations. A comparison of the interactions of 2′-AMP and 2′-GMP with RNase T1 reveals that Glu58 and Asn98 at the phosphate binding site and Glu46 at the base binding site preferentially stabilise the enzyme - 2′-GMP complex. 相似文献
3.
Tuncer Arslan Anil T. Abraham Sidney M. Hecht 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):515-530
Abstract A partial DNA duplex containing a high efficiency topoisomerase I cleavage site was substituted singly at each of three sites with 3′-deoxyadenosine. Depending on the site of substitution, the facility of the topoisomerase I-mediated cleavage or ligation reactions was altered. Inclusion of the modified nucleoside at the 5′-end of the acceptor oligonucleotide diminished the rate of religation following substrate cleavage by the enzyme. 相似文献
4.
Moon Woo Chun Sung Wook Choi Tae Kyung Kang Won Jun Choi Hea Ok Kim Zhan-Guo Gao 《Nucleosides, nucleotides & nucleic acids》2013,32(4):408-420
On the basis of high binding affinity of 3′-aminoadenosine derivatives 2b at the human A3 adenosine receptor (AR), 3′-acetamidoadenosine derivatives 3a–e were synthesized from 1,2:5,6-di-O-isopropylidene-D-glucose via stereoselective hydroboration as a key step. Although all synthesized compounds were totally devoid of binding affinity at the human A3AR, our results revealed that 3′-position of adenosine can only be tolerated with small size of a hydrogen bonding donor like hydroxyl or amino group in the binding site of human A3AR. 相似文献
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6.
Hideo Inoue Masaki Shimizu Takako Furukawa Takashi Tamura Miwa Matsui Eiko Ohtsuka 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1503-1505
Abstract 2′-Deoxy- and 2′-O-methyl-5′-O-terpyridyl derivatives of adenosine and cytidine were synthesized and used to construct 5′-end-modified oligonucleotides. These antisense agents complexed with Cu(II) exclusively cleaved a complementary RNA oligomer at the site opposite the terpyridine-nucleoside residue. We also found that the terpyridine·Cu(II) moiety stabilizes 2′-O-methyl RNA duplex. These suggest that after RNA hybridization, the terpyridine moiety is close to the RNA strand, presumably in an end capping manner. 相似文献
7.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):519-534
Abstract Ribonucleoside 5′-diphosphate reductases (RDPRs) have been studied for several decades. Increasingly sophisticated mechanisms have been proposed for the reduction of natural substrate ribonucleotides to their 2′-deoxy counterparts and for mechanism-based inactivation of RDPRs with 2′-substituted-ribonucleotides. We now discuss biomimetic reactions of model substrate and inhibitor analogues, which clarify three aspects of previously proposed mechanisms postulated to occur at the active site of RDPRs. 相似文献
8.
Yôichi Iida 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):311-317
Abstract Nucleotide sequences of the exon-intron junction in human α- And δ-globin genes were analyzed by the quantification method proposed previously. We further studied several mutants of α- and δ- thalassemiaso, where mutational changes occur around the 5′-splice junction of the first intron. These changes abolish the normal 5′-splice site completely, but activate a cryptic site lying in the first exon. Such behaviours were well explained in terms of our quantification analysis. 相似文献
9.
E. Hoffmann J. Schmidt J. Simon H. Ruterjans 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):757-761
Abstract The solution structure of RNase T1 and its complexes with 2′-GMP and. 3′-GMP have been investigated by combined use of 2D-NMR spectroscopy and restrained molecular dynamics calculations (MD). An analysis of the nuclear Overhauser effects (NOEs) observed indicates the presence of one a helix as well as of two antiparallel β sheets. Interaction of the nucleotides with the active site leads to changes of the backbone conformation of the amino acids involved. However, the interaction between the protein and 3′-GMP is not as strong as the interaction with 2′-GMP, possibly because of weaker binding. 相似文献
10.
Andres Jäschke Rolf Bald Eckhart Nordhoff Franz Hillenkamp Dieter Cech Volker A. Erdmann 《Nucleosides, nucleotides & nucleic acids》2013,32(9):1519-1529
Abstract Polyethylene glycols with degrees of polymerization from 5 to more than 100 were incorporated into synthetic oligoribonucleotides by automated solid phase synthesis at 3′-terminal, 5′-terminal and internal positions. The conjugates were characterized by chromatographic, electrophoretic and mass-spectrometric methods. The influence of coupling site, polymer size and number of coupled polymers per oligonucleotide on the molecular properties of the conjugates is investigated. 相似文献
11.
Panagiotis Ioannidis Björn Classon Bertil Samuelsson Ingemar Kvarnström 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1205-1218
Abstract Nucleoside analogues analogues1-(2′,3′-dideoxy-2′-C-hydroxymethyl-β-D-erythro-pentofuranos-yl)thymine (1), 2′,3′-dideoxy-2′-C-hydroxymethylcytidine (2), 2′,3′-dideoxy-2′-C-hydroxymethyladenosine (3), 1-(2′-C-azidomethyl-2′,3′-dideoxy-β-D-erythro-pento-furanosyl)thymine (4), 2′-C-azidomethyl-2′,3′-dideoxycytidine (5), and 2′3′-dideoxy-2′-C-methylcytidine (6) have been synthesized from (S)-4-hydroxymethyl-y-butyro-lactone (7) 相似文献
12.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1479-1482
Abstract We will insert a cleavage site in an oligodeoxynucleotide, which can be used for a selective and quantitative cleavage. For that reason we synthesized the four 5′-S-(4,4′-dimethoxytrityl)-mercapto-2′-deoxynucleotide-3′-O-(2-cyanoethoxydiisopropylamino)-phosphites ( 5a–d ). The cleavage of P-S and C-S bonds is described (Mag, M.; Lücking, S.; Engels, J.W. Synthesis and selective cleavage of an oligodeoxy-nucleotide containing a bridged internucleotide 5′-phosphorthioate linkage Nucleic Acids Res. 1991, 19 (7), 1437–1441; Marriott, J.H.; Mottahedeh, M.; Reese, C.B. 9-(4-methoxyphenyl)xanthen-9-thiol: A useful reagent for the preperation of thiols. Tetrahedron Lett. 1990, 31 (51), 7485–7488; Divakar, K.J.; Mottoh, A.; Reese, C.B.; Shanghvi, Y.S. Approaches to the synthesis of 2′ thio analogues of pyrimidine ribosides. J. Chem. Sc., Perkin Trans. 1 1990, 969–974). The oligodeoxynucleotides with an achiral bridged 5′-phosphorothioate linkage 5′-O-P-S-3′ are synthesized by the phosphoramidite procedure. 相似文献
13.
Ian S. Haworth Adrian H. Elcock Alison Rodger W. Graham Richards 《Journal of biomolecular structure & dynamics》2013,31(3):553-569
Abstract Molecular mechanics calculations and molecular dynamics simulations have been used to study the binding of the partially inserted major groove complex of A-[Ru(1,10-phenanthroline)3]2+ with DNA. Energy refinements of this complex showed a clear preference for binding at purine-3′,5′-pyrimidine sites over pyrimidine-3′,5′-purine sites. The basis for this difference is shown to be a slight change in the binding orientation induced by interchanging the purine and pyrimidine bases. This in turn provides for a better secondary interaction with the helix backbone at a point beyond the immediate binding site. It is this secondary interaction that provides the additional energetic stabilisation for complexes formed at purine-3′,5′-pyrimidine sites. Molecular dynamics simulations including explicit representation of solvent support these conclusions and provide an insight into the positional stability of the ligand at a particular site. Repuckering of specific deoxyribose rings to the C3′-endo conformation seems to be an important feature of the DNA/ligand complex. 相似文献
14.
Shinya KIKUCHI Tomohiro MAEKAWA Katsumaro MINAMOTO Keizo TANIGAWA 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1365-1372
Abstract 2′,3′-Dibromo-2′,3′-dideoxy-5′-O-trityl-2′,3′-secouridine (8) with sdKF gave the 3′,4′-didehydro-2,2′-anhydro nucleoside 9, which was deprotected to 10. Hydrolysis of 9 gave 3′,4′-didehydro-3′-deoxy-5′-O-trityl-2′,3′-secouridine (11a). Similarly, compound 9 with pyridinium halides gave the corresponding 2′-deoxy-2′-halo nucleosides (11b-d). Compound 11d with azide ion gave 2′-azido analogue 11e. Compound 9 with an excess amount of azide ion gave the 2′-azido triazole (13). 相似文献
15.
Peihua Shang Hua Wang Changmei Cheng Hongchao Zheng Yufen Zhao 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1272-1281
A general method is described for synthesizing 3′,5′-dithio-2′-deoxypyrimidine nucleosides 6 and 13 from normal 2′-deoxynucleosides. 2,3′-Anhydronucleosides 2 and 9 are applied as intermediates in the process to reverse the conformation of 3′-position on sugar rings. The intramolecular rings of 2,3′-anhydrothymidine and uridine are opened by thioacetic acid directly to produce 3′-S-acetyl-3′-thio-2′-deoxynucleosides 3 or 5. To cytidine, OH? ion exchange resin was used to open the ring and 2′-deoxycytidine 10 was abtained in which 3′-OH group is in threo-conformation. The 3′-OH is activated by MsCl, and then substituted by potassium thioacetate to form the S,S′-diacetyl-3′,5′-dithio-2′-deoxycytidine 12. The acetyl groups in 3′,5′ position are removed rapidly by EtSNa in EtSH solution to afford the target molecules 6 and 13. The differences of synthetic routes between uridine and cytidine are also discusssed. 相似文献
16.
Abdalla Elsayed A. Hassan Satoshi Shuto Akira Matsuda 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):197-211
Abstract Reaction of 2′-deoxy-2′-methylidene-5′-O-trityluridine (1) with diethylamino-sulfur trifluoride (DAST) in CH2Cl2 resulted in the formation of a mixture of (3′R)-2′,3′-dideoxy-3′-fluoro-2′-methylidene derivative 3 and 2′,3′-didehydro-2′,3′-dideoxy-2′-fluoromethyl derivative 4 (3:4 = 1:1.5) in 65% yield. A similar treatment of 1-(2-deoxy-2-methylidene-5-O-trityl-β-D-threo-pentofuranosyl)uracil (19) with DAST in CH2Cl2 afforded (3′S)-2′,3′-dideoxy-3′-fluoro-2′-methylidene derivatives 20 and 4 in 38% and 17% yields respectively. Transformation of the uracil nucleosides 4, 12, and 20 into cytosines followed by deprotection furnished the corresponding cytidine derivatives 29, 18, and 25, respectively. The corresponding thymidine congener 27 was also synthesized in a similar manner. All of the newly synthesized nucleosides were evaluated for their inhibitory activities against HIV and for their antiproliferative activities against L1210 and KB cells. 相似文献
17.
Ruth Nussinov 《Journal of biomolecular structure & dynamics》2013,31(6):1051-1064
Abstract Several 3′ splice signals are known todate. At the 3′ splice site an AG doublet is frequently found. Just upstream of the splice site there is a string of 6–11 pyrimidines. More recently it has been found that one of the stages in the splicing process involves formation of a lariat, in which the 5′ end of the intron forms a 2′-5′ branch with an A residue located 18–37 nucleotides upstream of the 3′ splice site. The branching-point consensus is weakly defined and consists of the sequence YNYTRAY, where Y is a pyrimidine, R a purine and N any base. The A in the sixth position is the one with which branching occurs. Here we present the results of extensive searches for additional putative signals around the branching-point consensus and the 3′ splice site in rodent nuclear precursor mRNAs. The signals obtained for the over 370 rodent introns are compared with those found in a larger eukaryotic sample containing over 900 nuclear pre-mRNA introns. Of particular interest are GGGA and CCCA In both analyses GGGA occurs about 60 nucleotides upstream and CCCA is found 3–40 nucleotides downstream from the 3′ splice site. A model explaining some of the putative signals discussed here is also proposed. This model involves formation of alternate stem-loop structures around the branching point and 3′ splice site. Such signals and structures can possibly aid in protein or nucleoprotein branching point and splice site recognition. 相似文献
18.
Akira Matsuda Hitomi Okajima Akira Masuda Akio Kakefuda Yuichi Yoshimura Tohru Ueda 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):197-226
Abstract New methods for the synthesis of 2′,3′-didehydro-2′,3′-dideoxy-2′ (and 3′)-methyl-5-methyluridines and 2′,3′-dideoxy-2′ (and 3′)-methylidene pyrimidine nucleosides have been developed from the corresponding 2′ (and 3′)-deoxy-2′ (and 3′)-methylidene pyrimidine nucleosides. Treatment of a 3′-deoxy-3′-methylidene-5-methyluridine derivative 8 with 1,1′-thiocarbonyldiimidazole gave the allylic rearranged 2′,3′-didehydro-2′,3′-dideoxy-3′-[(imidazol-1-yl)carbonylthiomethyl] derivative 24. On the other hand, reaction of 8 with methyloxalyl chloride afforded 2′-O-methyloxalyl ester 25. Radical deoxygenation of both 24 and 25 gave 26 exclusively. Palladium-catalyzed reduction of 2′,5′-di-O-acetyl-3′-deoxy-3′-methylidene-5-methyluridine (32) with triethylammonium formate as a hydride donor regioselectively afforded the 2′,3′-dideoxy-3′-methylidene derivative 35 and 2′,3′-didehydro-2′,3′-dideoxy-3′-methyl derivative 34 in a ratio of 95:5 in 78% yield. These reactions were used on the corresponding 2′-deoxy-2′-methylidene derivatives. An alternative synthesis of 2′,3′-dideoxy-2′-methylidene pyrimidine nucleosides (43, 52, and 54) was achieved from the corresponding 1-(3-deoxy-β-D-thero-pentofuranosyl)pyrimidines (44 and 45). The cytotoxicity against L1210 and KB cells and inhibitory activity of the pathogenicity of HIV-1 are also described 相似文献
19.
Daguang Wang Bin Meng Masad J. Damha George Just 《Nucleosides, nucleotides & nucleic acids》2013,32(9-10):1961-1984
Abstract 3′-Deoxy-3′-(2-mesyloxyethyl)ribofuranosylthymine derivative 3, and its 2′-methoxy (16) and 2′-deoxy (38) analogs were condensed with 5′-deoxy-5′-thiothymidine 4 and 17 or 2′-O-methyl-5′-deoxy-5′-thiouridine 34 and 37 to provide, after standard functional group transformations, thymidine-thymidine and uridine-thymidine dimers 9, 21, 43 and 47. Oxidation of model sulfide dimer 48 with oxone gave sulfone 49. It was not stable to 27% ammonia. 相似文献
20.
Serge Van Calenbergh Adriaan P. IJzerman Piet Herdewijn 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1571-1576
Abstract Full adenosine A1 receptor agonists like CPA and other N 6-?substituted adenosine analogs have previously been shown to become partial agonists upon deletion of the 3′-hydroxyl moiety. The present study further explored the C-3′ site for modification. The modest affinity at A1 and A2a receptors found in the 3′-amido-3′-deoxyxyIofuranosyladenine series prompted us to synthesize the corresponding N 6-?cyclopentyl derivatives, which proved to exhibit potent antagonistic behaviour at the A1 receptors. This represents a new perspective in the purinergic field. 相似文献