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1.
《Bioorganic & medicinal chemistry letters》2014,24(22):5318-5320
A new series of glycosyl oxadiazoles compounds were synthesized and characterized through 1H NMR, 13C NMR, IR and HRMS. The anti-tumor activities for MDA-MB-231 of all these new compounds were screened in vitro by MTT assay. Due to the modification of gastrodin analogues, the anti-tumor activities of these 1,3,4-oxadiazoles derivatives were greatly improved. Six compounds (6c, 6d, 6i, 6j, 6k and 6l) displayed relatively higher MDA-MB-231 potency with IC50 values (0.89, 0.26, 1.35, 3.60, 0.95 and 1.08 μM) compared with the reference medicine Rosiglitazone (5.23 μM). 相似文献
2.
《Bioorganic & medicinal chemistry letters》2014,24(12):2703-2706
A cyclic form of N6-threonylcarbamoyladenosine bearing an oxazolone moiety (ct6A) was discovered very recently at the position 37 in several tRNA sequences. Our study on the synthesized 5′,3′,2′-O-acetylated derivative of ct6A confirmed high stability of the modified nucleoside under physiological conditions (PBS buffer, pH 7.4) and revealed remarkable stability of the oxazolone ring in acidic (100 mM HCl, pH 1) and basic (0.1 mM NaOH, pH 10) conditions. This feature may allow for the post-synthetic conversion of t6A into ct6A in assembled oligoribonucleotides. 相似文献
3.
《Redox report : communications in free radical research》2013,18(5):208-212
AbstractInduction of DNA damage by pyrogallol has been shown at physiological pH, but mutagenesis data also suggest there is inhibition in acidic media. In the present work, the plasmid pBSK was incubated with pyrogallol, under aerobic conditions at 37°C, at pH 7.4, 4.5 or 3.5, for 1, 3 or 5 h, in the absence or presence of Cu2+. Cleavage of the supercoiled DNA form was analyzed through topology modifications by agarose gel electrophoresis and quantified by densitometry. Independently of the presence of Cu2+ , DNA cleavage at pH 7.4 was significantly (P < 0.001) induced and occurred extensively after 1-h incubation. At pH 4.5, the cleavage was significantly (P < 0.05) induced only after 5 h incubation in the absence of Cu2+ , but was extensive (P < 0.001) after 1-h incubation when the metal ion was present. At pH 3.5, DNA cleavage was inhibited (P > 0.05), after 5-h incubation, even in the presence of Cu2+. Our results provide evidence that DNA cleavage by pyrogallol is pH-dependent, catalyzed by Cu2+ , and extensively decreased in acidic pH. Due to the abundant presence of the pyrogallate ion in physiological media, we suggest that this conjugate base form is responsible for DNA cleavage. 相似文献
4.
《Biocatalysis and Biotransformation》2013,31(2):173-186
Based on an unexpected transformation of N (1)-(2-aminoethyl)-NAD(P) to N6-(2-aminoethy1)-NAD(P) under mild aqueous conditions (pH 6.0-6.5, 50°C) synthesis of uniform macromolecular derivatives of N6-alkylated NAD and N6-alkylated NADP was possible, with, in most cases, acceptable overall yields (6-37%). The usual steps of (a) the chemical reduction with Na2S2O4,(b) the Dimroth rearrangement under harsh alkaline conditions and (c) the enzymatic or chemical oxidation were omitted. This represents a significant simplification of the procedure. A common procedure for the synthesis of macromolecular N6-(2-aminoethyl)-NAD(P) derivatives was pursued, coupling N6-(2-aminoethyl)-NAD(P) to several water-soluble copolymers containing maleic acid anhydride. PEG (Mr = 20000)-N6-(2-aminoethl)-NAD, polyvinylpyrrolidone (Mr,= 160000)-N6-(2-aminoethylNAD and dextran (Mr= 70000)-N6-(2-aminoethyl)-NAD were synthesized by covalently binding N6-(2-aminoethyl)-NAD to the corresponding carboxylated polymers by the carbodiimide method. PEG (Mr= 4000 and 20000-N6-(2-aminoethyl)-NADP was efficiently synthesized by covalent attachment of N6-(2-aminoethyl)-NADP to N-hydroxy-succinimide activated carboxylate PEG (Mr= 4000 and 20000), avoiding the carbodiimide method, which would lead simultaneously to 2′3′-cyclic NADP derivatives. Except for the macromolecular cofactor derivatives based on copolymers containing maleic acid anhydride, the total enzymatic reducibility of the macromolecular N-(2-aminoethyl)-NAD(P) derivatives was satisfactory (90-95%). 相似文献
5.
Keramida Maria Matsoukas John M. Agelis George Panagiotopoulos Dimitris Cladas John Pati Debanada Moore Graham J. Habibi Hamid R. 《International journal of peptide research and therapeutics》1998,5(4):305-315
Summary We have recently reported the synthesis and the conformational properties of some Gonadotropin-releasing hormone (GnRH) analogues
in which the tyrosine residue at position 5 is substituted with tyrosine-O-methyl (Keramida et al., Let. Pept. Sci., 3 (1996)
257/Matsoukas et al., Eur. J. Med. Chem., 32 (1997) 927). The analogue [Tyr-(OMe)5]-GnRH was found to exert a lower degree of desensitization than the native GnRH peptides in terms of pituitary gonadotropin
(GTH) release in goldfish. Compared to GnRH, however, [Tyr-(OMe)5]-GnRH exerted a lower GTH-release potency in cultured goldfish pituitary fragments, and was bound with a lower binding affinity
to the rat pituitary GnRH receptors. In order to increase the potency of [Tyr-(OMe)5]-GnRH, we have synthesized a group of GnRH peptides containing Tyr-(OMe)5 in combination with other substitutions at positions 6, 9 and 10 and we have estimated their binding affinity for the rat
pituitary receptors and gonadotropin (GTH) release potency in the goldfish pituitary. A selected number of these analogues
was also tested for their ability to induce ovulation in seabass. The important structural modifications that increased the
binding and gonadotropic activity of [Tyr(OMe)5]-GnRH in vitro and in vivo were found to include the replacement of the proline at position 9 with azetidine, glycine amide
terminus with an alkyl amide group and Gly6 residue with hydrophilicd-amino acids such asd-Arg6. Overall, the findings provide SAR information on a group of novel GnRH peptides that can be also used to induce ovulation
in teleosts. 相似文献
6.
Aikaterini A. Zompra Vassiliki Magafa Dimitra G. Chryssanthi Fotini N. Lamari Georgios A. Spyroulias Theodosia Maina Berthold A. Nock Nikos K. Karamanos Paul Cordopatis 《International journal of peptide research and therapeutics》2007,13(1-2):143-149
GnRH analogues have been extensively used in oncology to induce reversible chemical castration due to their hypophysiotropic
action. In addition to that, it has recently been shown that many malignant cells, such as breast cancer cells, locally produce
GnRH and express the GnRH receptor/s. In order to investigate the structure-activity relationships in both pituitary and extrapituitary
biological systems, we synthesized eight new GnRH analogues with modifications in the N-terminal part and/or in position 6
and studied their pituitary binding affinity (in αT3-1 cell membranes) and effect on breast cancer (MCF-7) cell proliferation.
2-Amino-4-pyrrolidinothieno[2,3-d]pyrimidine-6-carboxylic acid (ATPC) was incorporated instead of pGlu1-His2- and/or Gly6 was substituted by α-aminoisobutyric acid, D-Leu and D-Lys (alone or covalently linked to Gly, Ala, Sar, ATPC). Most GnRH
analogues lacked the carboxy-terminal Gly10-amide of GnRH and an ethylamide residue was added to Pro9, a modification common in many potent GnRH agonists, such as leuprolide ([D-Leu6, des-Gly10]-GnRH-NHEt. Results show differential impact of these modifications on the binding affinity to the GnRH receptor in mouse
pituitary cells and on the inhibition of human breast cancer cell proliferation. ATPC in the N-terminus resulted in analogues
with low binding affinity but high antiproliferative effect. Substitutions in position 6 always resulted in high binding affinities.
In particular, [D-Lys6(Gly), desGly10]-GnRH-NHEt and [D-Lys6(Sar), desGly10]-GnRH-NHEt have higher pituitary binding affinity than leuprolide, but only the latter had significant antiproliferative
effect on both MCF-7 and MDA-MB-231 cells. These results contribute to the on-going research for more potent GnRH analogues.
Abbreviations of common amino acids are in accordance with the recommendations of IUPAC-IUB Joint Commission on Biochemical
Nomenclature: Arch. Biochem. Biophys. 206, pp.v-xxii (1988), J. Biol. Chem. 264, 668–673 (1989) or J. Peptide Sci. 9, 1–8
(2003). 相似文献
7.
Shuping Dou John Virostko Dale L. Greiner Alvin C. Powers 《Nucleosides, nucleotides & nucleic acids》2015,34(2):69-78
Synthetic DNA analogues with improved stability are widely used in life science. The 3′and/or 5′ equivalent terminuses are often derivatized by attaching an active group for further modification, but a certain amount of non-derivatized impurity often remains. It is important to know to what extent the impurity would influence further modification. The reaction of an NHS ester with primary amine is one of the most widely used options to modify DNA analogues. In this short communication, a 3′-(NH2-biotin)-derivatized morpholino DNA analogue (MORF) was utilized as the model derivatized DNA analogue. Inclusion of a biotin concomitant with the primary amine at the 3′-terminus allows for the use of streptavidin to discriminate between the products from the derivatized MORF and non-derivatized MORF impurity. To detect the MORF reaction with NHS ester, S-acetyl NHS-MAG3 was conjugated to the DNA analogue for labeling with 99mTc, a widely used nuclide in the clinic. It was found that the non-derivatized MORF also reacted with the S-acetyl NHS-MAG3. Radiolabeling of the product yielded an equally high labeling efficiency. Nevertheless, streptavidin binding indicated that under the conditions of this investigation, the non-derivatized MORF was five times less reactive than the amine-derivatized MORF. 相似文献
8.
D. M. Kolpashchikov L. A. Alexandrova N. F. Zakirova S. N. Khodyreva O. I. Lavrik 《Russian Journal of Bioorganic Chemistry》2000,26(2):134-137
A new reagent for photoaffinity modification of biopolymers, 5-[E-N-(2-nitro-5-azidobenzoyl)-3-amino-1-propen-1-yl]-2′,3′-dideoxyuridine 5′-triphosphate (NAB-ddUTP), was synthesized. Like a
similar derivative of 2′-deoxyuridine 5′-triphosphate (NAB-dUTP), it was shown to be able to effectively substitute for dTTP
in the synthesis of DNA catalyzed by eukaryotic DNA polymerase β and to terminate DNA synthesis. A 5′-32P-labeled primer with a photoreactive group at the 3′-terminus was derived from NAB-ddUTP and used for photoaffinity labeling
of the human replication protein A (RPA). The covalent attachment of RPA p32 and p70 subunits to the labeled primers was demonstrated.
NAB-ddUTP is a promising tool for studying the interaction of proteins of the replicative complex with NA in cellular extracts
and living cells during the termination of DNA synthesis. 相似文献
9.
The incorporation of [3H]UTP into RNA by isolated polytene salivary gland nuclei of Chironomus thummi was investigated under different incubation conditions; the labeled RNA fractions were characterized by electrophoresis. The results suggested that at two characteristic ionic conditions most of the RNA synthesized was the product of RNA polymerase I or RNA polymerase II as distinguished by their differential sensitivities to α-amanitin. Electrophoretical analysis of the RNA synthesized under conditions favouring polymerase I showed that this RNA population consisted mainly of four distinct molecular weight fractions within a range between 2.8 × 104 and 2.5 × 106. Under conditions favouring polymerase II two fractions were detected: one with a broad molecular weight distribution around 0.4 × 106 containing considerable amounts of poly(A)-bearing RNA molecules, and a second with a peak at a molecular weight of 2.8 × 104. 相似文献
10.
11.
WHEN the replication of density-inhibited cultures of fibroblasts1,2 is stimulated by a change of medium3–5, the rate of nuclear acidic protein synthesis10–13 is immediately increased. We wanted to determine whether the induction of cellular DNA synthesis by an oncogenic virus6–9 is also preceded by nuclear acidic protein synthesis. We report here the effect of SV40 virus infection of a permissive and a non-permissive cell line on their synthesis of total cellular proteins and nuclear acidic proteins in the first hours after infection. 相似文献
12.
Yang Yue Jing Li Ji Zhang Zhong‐Wei Zhang Hong‐Hui Lin Shan‐Yong Chen Xiao‐Qi Yu 《化学与生物多样性》2009,6(12):2236-2243
Two dinuclear macrocyclic polyamine copper(II) (CuII) complexes, which have two cyclen units linked by urea, were synthesized as DNA‐cleavage agents. The structures of these new dinuclear complexes were identified by HR‐ESI‐MS and IR analyses. The catalytic activities of DNA cleavage of these dinuclear CuII complexes were subsequently studied. The results show that 6a was the better catalyst in the DNA‐cleavage process than 6b . The effects of reaction time and concentration of complexes were also investigated. The results indicate, that the CuII complexes could catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA; Form I) under physiological conditions to produce selectively nicked DNA (Form II; no Form III was produced) with high yields (nearly 100%) in short time in the absence of reductant or oxidant. 相似文献
13.
Polymerase-mediated single-base extension (SBE) of primers using a fluorescently labeled 2′,3′-dideoxynucleotide triphosphate terminator was originally commercialized as SNaPshot for analysis of single-nucleotide polymorphisms by capillary electrophoresis (CE). Application of this general method to bisulfite-converted/PCR-amplified genomic DNA (gDNA) to analytically infer polymorphic methylation status (i.e., 5-methylcytosine [5mC] vs. cytosine [C]) in CpG-rich regions of gDNA has been noted previously by others to be limited by CE mobility-shifted peaks for SBE products derived from guanine (G)/adenine (A)-mixed-base primers used to hybridize to possible polymorphic sites (i.e., C vs. thymine [T] resulting from 5mC vs. C, respectively). This limitation is precluded in the current study by using novel SNaPshot primers modified with N6-methoxy-2,6-diaminopurine (K), which was originally described in 1991 by Brown and Lin as a unique adenine–guanine analog capable of participating in three H-bonds with C or T in DNA. Oligonucleotides modified by K as a bispecific complement for C/T are commercially available or can be readily synthesized, and they may have utility in other assay formats used to analyze CpG methylation status. 相似文献
14.
Two novel coordination compounds of half-sandwiched ruthenium(II) containing 2-(5-fluorouracil)-yl-N-(pyridyl)-acetamide were synthesized, and their intercalation binding modes with calf thymus DNA were revealed by hyperchromism of ultraviolet-visible spectroscopy; the binding constants were determined according to a Langmuir adsorption equation that was deduced on the base of careful cyclic voltammetry measurements. The two compounds exhibited DNA intercalation binding activities with the binding constants of 1.13×106 M-1 and 5.35 ×105 M-1, respectively. 相似文献
15.
Yong-Zhe Xiang Li-Hong Zhou Ning Jiang Hong-Hui Lin 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):315-319
The novel linear polymer of a macrocyclic polyamine copper (II) complex, which has many cyclen groups linked by epichlorohydrin, has been synthesized as a DNA cleavage agent. The structure of the polymer 3 was identified by 1HNMR and IR and its molecular weight was measured by GPC. The result of agarose gel electrophoresis assay showed that Cu-(II) complex 4 could act as a powerful catalyst for the cleavage of plasmid DNA under physiological conditions. 相似文献
16.
《Journal of inorganic biochemistry》1999,73(1-2):117-122
A novel ruthenium(II) complex of dipyridophenazine (DPPZ) with the ancillary ligand imidazole[4,5-f] [1,10]phenanthroline (IP), [Ru(IP)2(DPPZ)] (PF6)2, has been synthesized and characterized by elemental analysis, 1D and 2D 1H NMR, fast-atom bombardment mass spectra (FABMS), electronic spectroscopy and cyclic voltammetry. The DNA-binding properties of the complex were studied by spectroscopic methods. The intrinsic binding constant, K =2.1 × 107M−1, of the complex to calf thymus DNA has been determined by absorption titration in 5 mmol dm−3 Tris-HCl, 50 mmol dm−3 NaCl buffer (pH 7.0). The excited state lifetimes and luminescence quenching with [Fe(CN)6]4− as the quencher in the presence of DNA were also tested and mono-exponentiality was observed for the emission decay curves. Viscosity measurements together with the optical titrations unambiguously proved that the complex bound with DNA intercalatively and that the binding affinity to DNA was several times larger than that of the parent complex [Ru(bpy)2(DPPZ)]2+. 相似文献
17.
18.
M. Helena Garcia Andreia Valente Tânia S. Morais M. Teresa Duarte Francesc X. Avilés 《Inorganica chimica acta》2010,363(14):3765-3775
A new family of Ru(II) mixed metallocene complexes of the type [Ru(η5-C5H5)(η6-arene)][PF6] has been synthesized and fully characterized by NMR and UV-Vis spectroscopy. X-ray analysis of single crystal was achieved for all the complexes and revealed the presence of two enantiomers expected for planar chirality originated by the η6 coordination of the arene prochiral ligands. Studies of interaction of the new complexes with pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed low antiproliferative activity compared to cisplatin. 相似文献
19.
《Bioorganic & medicinal chemistry letters》2014,24(15):3559-3564
A novel series of Cu(II), Ni(II), Zn(II), Co(II), and Cd(II) complexes have been synthesized from the Schiff base. Structural features were determined by analytical and spectral techniques like IR, 1H NMR, UV–vis, elemental analysis, molar electric conductibility, magnetic susceptibility and thermal studies. The complexes are found to be soluble in dimethylformamide and dimethylsulfoxide. Molar conductance values in dimethylformamide indicate the non-electrolytic nature of the complexes. Binding of synthesized complexes with calf thymus DNA (CT DNA) was studied. There is significant binding of DNA in lanes 2, 3, and 5. Lanes 4 and 6 are showing more florescence when compared to the control indicating that these molecules are strongly bound to the DNA by inserting themselves between the two stacked base pairs and exhibiting their original property of fluorescence. Angiogenesis study has revealed that the compounds B-2, B-4 and B-5 have potent antitumor efficacy and activation of antiangiogenesis could be one of the possible underlying mechanisms of tumor inhibition. 相似文献
20.
Lebedeva NA Kolpashchikov DM Rechkunova NI Khodyreva SN Lavrik OI 《Biochemistry. Biokhimii?a》2002,67(7):807-814
A binary system of photoaffinity reagents was proposed earlier for highly efficient labeling of DNA polymerases by 5"-[32P]DNA primers. In the present study we demonstrate the feasibility of this approach to increase the efficiency of DNA polymerase labeling. A photoactive 2,3,5,6-tetrafluoro-4-azidobenzoyl (FAB) group was incorporated at the 3"-end of 5"-[32P]DNA primers synthesized by DNA polymerase or Tte in the presence of one of the dTTP analogs—FAB-4-dUTP, FAB-9-dUTP, or FAB-4-ddUTP. The reaction mixture was irradiated by light with wavelength of 334-365 nm (direct labeling) or 365-450 nm in the presence of photosensitizer, one of dTTP analogs containing a pyrene moiety, Pyr-6-dUTP or Pyr-8-dUTP. In the case of the binary system of photoaffinity reagents, a FAB group is activated by energy transfer from sensitizer localized in the dNTP-binding site of DNA polymerase in the triple complex, comprised by reagent, DNA polymerase, and Pyr-6(8)-dUTP. Direct activation of the FAB group under these conditions is negligible. The most efficient photolabeling of DNA polymerases was observed with a primer containing a FAB-4-dUMP group at the 3"-end, and Pyr-6-dUTP as a photosensitizer. Using 10-fold molar excess of photoreagent to DNA polymerase , the labeling efficiency was shown to achieve 60%, which is 2-fold higher than the efficiency of the direct DNA polymerase labeling under harsher conditions (334-365 nm). 相似文献