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61.
N J Prakash G F Davis E T Jarvi M L Edwards J R McCarthy T L Bowlin 《Life sciences》1992,50(19):1425-1435
S-Adenosylhomocysteine hydrolase (AdoHcy-nase) is a key enzyme in transmethylation reactions. The objective of the present study was to examine the potential antiretroviral activities of novel mechanism-based irreversible AdoHcy-nase inhibitors. (Z)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (ZDDFA), (E)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (EDDFA), (Z)-4',5'-didehydro-5'-deoxy-5'-chloroadenosine (ZDDCA) and 5'-deoxy-5'-acetylenic adenosine (DAA) inhibited AdoHcy-nase activity with Ki values of 0.55, 1.04, greater than 10.0 and 3.30 microM, respectively. These four compounds were tested for antiviral activity in vitro against Moloney leukemia virus (MoLV) in the XC-plaque assay. MoLV replication in murine fibroblasts (SC-1) was inhibited by ZDDFA, EDDFA and DAA with IC50 values of 0.05, 0.25 and 3.30 micrograms/ml, respectively. ZDDCA did not inhibit MoLV infection at the concentrations tested. Antiviral activity correlated with the ability of the individual compounds to maintain sustained elevations in intracellular S-adenosylhomocysteine (AdoHcy) concentrations in the SC-1 cells. ZDDFA, the most potent inhibitor of AdoHcy-nase and MoLV was also the most active in maintaining sustained elevations in intracellular AdoHcy levels. The antiviral activity of ZDDFA was also examined in murine C3H1OT1/2 fibroblasts which constitutively produce MoLV. Pretreatment with ZDDFA (1.0 microgram/ml) for 24 hr inhibited virus production by 88%. Similar to the SC-1 cells, and concomitant with enzyme inhibition, there was a 300-fold increase in AdoHcy levels in ZDDFA (1.0 microgram/ml) treated C3H1OT1/2 cells. Incorporation of a [3H]methyl group from tritiated S-adenosylmethionine into total RNA in C3H1OT1/2 cells was inhibited by ZDDFA without affecting cell viability. These results suggest that mechanism-based inhibitors of AdoHcy-nase, such as ZDDFA, may have potential as antiretroviral agents. 相似文献
62.
The investigation of the effect of acid pH on the structure of beta-globulin indicated several transitions as a function of pH. Upon reducing the pH from 7.0, the beta-globulin molecule underwent an expansion due to hydration up to pH 5.0, and a further increase in H+ concentration resulted in unfolding. This is a single step cooperative denaturation as indicated by the viscosity profile. At extreme acid pH values (below pH 2.0) the protein associates or folds to a different conformational motif as shown by blue shift of ultraviolet fluorescence emission maximum and decrease in reduced viscosity values by more than 30% due to an entropically driven hydrophobic interaction. The conformational analysis of beta-globulin showed a decrease up to pH 3.0, followed by an increase in the ordered structure at low pH values indicating that the low pH values stabilized this new conformation. These results are discussed in view of the molten globule structure of proteins. 相似文献
63.
A rapid and efficient method for the extraction of total DNA from the sweet potato and its related species 总被引:2,自引:2,他引:0
Secondary metabolites, latex/mucilagenous secretions, polysaccharides, and proteins interfere with the extraction of high-quality,
restrictable total cellular DNA from sweet potato [Ipomoea batatas (L.) Lamk.] and related species. A method for the DNA extraction is described which overcomes these problems. 相似文献
64.
DNA-directed alkylating ligands as potential antitumor agents: sequence specificity of alkylation by intercalating aniline mustards 总被引:3,自引:0,他引:3
A S Prakash W A Denny T A Gourdie K K Valu P D Woodgate L P Wakelin 《Biochemistry》1990,29(42):9799-9807
The sequence preferences for alkylation of a series of novel parasubstituted aniline mustards linked to the DNA-intercalating chromophore 9-aminoacridine by an alkyl chain of variable length were studied by using procedures analogous to Maxam-Gilbert reactions. The compounds alkylate DNA at both guanine and adenine sites. For mustards linked to the acridine by a short alkyl chain through a para O- or S-link group, 5'-GT sequences are the most preferred sites at which N7-guanine alkylation occurs. For analogues with longer chain lengths, the preference of 5'-GT sequences diminishes in favor of N7-adenine alkylation at the complementary 5'-AC sequence. Magnesium ions are shown to selectively inhibit alkylation at the N7 of adenine (in the major groove) by these compounds but not the alkylation at the N3 of adenine (in the minor groove) by the antitumor antibiotic CC-1065. Effects of chromophore variation were also studied by using aniline mustards linked to quinazoline and sterically hindered tert-butyl-9-aminoacridine chromophores. The results demonstrate that in this series of DNA-directed mustards the noncovalent interactions of the carrier chromophores with DNA significantly modify the sequence selectivity of alkylation by the mustard. Relationships between the DNA alkylation patterns of these compounds and their biological activities are discussed. 相似文献
65.
V. Prakash 《Journal of biosciences》1982,4(3):347-359
The interaction of α-globulin with urea/guanidine hydrochloride was investigated by determining the apparent partial specific
volumes of the protein in these solvents. The apparent partial specific volumes were determined both under isomolal and isopotential
conditions. The preferential interaction parameter with solvent components calculated were 0.08 and 0.1 g of urea and guanidine
hydrochloride respectively per g protein. In both the cases the interaction was not preferential with water. The total binding
of denaturant to α-globulin was calculated both for urea and guanidine hydrochloride and the correlation between experimentally
determined number of mol of denaturant bound per mol of protein and the total number of peptide bonds and aromatic amino acids
were found to be in excellent agreement with each other. The changes in volume upon transferring α-globulin from a salt solution
to 8 M urea and 6 M guanidine hydrochloride were also calculated.
This work was done at the Biochemistry Department, Brandeis University, Waltham, Massachusetts 02254, USA. 相似文献
66.
Observations on morphological characters of milk and permanent teeth, based on 648 pairs of dental casts of 356 male and 292 female Jat children of Haryana (India) are reported. Deciduous teeth show high frequencies of bilateral winging of maxillary central incisor, Carabelli's cusp of maxillary second molar, and deflecting wrinkle of mandibular second molar. Reduction of maxillary molar cusps is more marked in males than in females. Y pattern is very common in deciduous molars. Permanent teeth have high frequencies of grooved cingulum of incisors, cingular nodule of lateral incisors and canines, and distal accessary ridge of canines. Low frequencies of Carabelli's cusp and winging are also common. The tendency towards faintly developed shovelling in milk incisors occurs more often than in the permanent teeth. 相似文献
67.
α-Galactosidase from Vicia faba seeds has been resolved into three molecular forms, I, II1 and II2, respectively. Enzyme I is a tetramer (Mr 160 000) consisting of identical sub-units (Mr 44000 ± 2000). All three forms display lectin activity with glucose/mannose specificity. Enzyme I has been further studied with respect to its lectin specificity and various factors affecting this property. The results indicate that the catalytic and the lectin sites reside in the same protein molecule. The results presented are unique in that the enzyme activity is specific for galactose and its lectin activity is specific for glucose/mannose. 相似文献
68.
Louise Prakash 《Molecular & general genetics : MGG》1981,184(3):471-478
Summary Postreplication repair of nuclear DNA was examined in an excision defective haploid strain of yeast lacking mitochondrial DNA (ral 0). The size of the DNA synthesized in cells exposed to various fluences of ultraviolet light (UV) corresponds approximately to the average interdimer distance in the parental DNA. Upon further incubation of cells following exposure to 2.5 J/m2, the DNA increases in size; by 4 h, it corresponds to DNA from uniformly labeled cells. The alkaline sucrose sedimentation pattern of DNA pulse labeled at various times after UV irradiation, for up to 4 h, does not change substantially, indicating that dimers continue to block DNA replication. A significant amount of postreplication repair requires de novo protein synthesis, as determined by its inhibition by cycloheximide. The rad6 mutant does not carry out postreplication repair, the rad18 and rad52 mutants show great inhibition while the rev3 mutation does not affect postreplication repair. Both recombinational and nonrecombinational repair mechanisms may function in postreplication repair and most of postreplication repair is error free. 相似文献
69.
Madhavi Ratnam Prakash Najma Zaheer Baquer 《Biochemical and biophysical research communications》1980,94(3):849-854
The effect of intraperitoneal injection of imipramine hydrochloride on the activity of gamma-aminobutyric acid transaminase was determined in three regions of the rat brain.The cerebral hemispheres did not show a significant change in the activity of gamma-aminobutyric acid transaminase. Cerebellum and brain stem, both, however, showed a very significant decrease in the activity of the enzyme at 15 and 30 minutes after drug administration. At 90 minutes after drug administration, the activity of gamma-aminobutyric acid transaminase had returned to nearly control values. 相似文献
70.