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Biomedical subjects

S M Hecht

Publications and source records attributed to S M Hecht.

158 records · Page 9Linked to original sources
PubMed1969

Cytokinins: synthesis, mass spectra, and biological activity of compounds related to zeatin.

Compounds related to dihydrozeatin that define the influence of the location of the hydroxyl group along the side chain have been synthesized and tested for cytokinin activity. The compounds compared are in the series: 6-(X-hydroxy-3-methylbutylamino)purines and their ribosides, where X = 2, 3, and 4.Hydroxy substitution on the 4-position of the side chain enhances, but in the 2-, 3-, or 2- and 3- positions, decreases cytokinin activity as compared with the unsubstituted isopentyl (or isopentenyl) chains. This differential influence of the position of the hydroxyl group in the N(6)-chain holds also for the similarly related 9-beta-D-ribofuranosides. The relatively higher activity of 3,4-dihydroxy as compared with 2,3-dihydroxy derivatives is consistent with this position effect.Compounds related to zeatin possessing side-chain ester moieties have also been synthesized and tested comparatively. Among these, 6-(4-acetoxy-3-methyl-trans-2-butenylamino)purine is at least as active as zeatin, the most active presently known cytokinin in the tobacco bioassay, whereas the analog, methyl 2-methyl-4-(purin-6-ylamino)-trans-crotonate, with the ester function effectively reversed, has vastly lower activity, and its riboside is practically inactive.

Journal Article↗
PubMed1968

Cytokinin from soluble RNA of Escherichia coli: 6-(3-methyl-2-butenylamino)-2-methylthio-9-beta-D-ribofuranosylpurine.

We have isolated a compound responsible for the cytokinin activity of soluble RNA from Escherichia coli. The structure, indicated as 6-(3-methyl-2-butenylamino)-2-methylthio-9-beta-D-ribofuranosylpurine, C(16)H(23)N(5)0(4)S, on the basis of low-and high-reso!ution mass spectrometry, was established by unequivocal synthesis. The mass spectra, chromatographic behavior, and ultraviolet spectra of the compounds from natural and synthetic sources were identical.

Chromatography, Paper↗
PubMedDate not supplied

High-field 1H-NMR spectral analysis of some cucurbitacins.

1H-nmr spectra of the natural products cucurbitacins A, B, C, D, E, F, I, L, 23, 24-dihydrocucurbitacin F, and hexanorcucurbitacin F, as well as three acetylated derivatives, were measured at 360 MHz in pyridine-d5. Chemical shifts and coupling constants were tabulated. In addition to all of the ring and side-chain protons, it was possible to assign several of the hydroxy group signals of these compounds. These compiled data should be useful for the structure determination of new compounds in this series.

Cucurbitacins↗
PubMedDate not supplied

DNA strand scission by bleomycin group antibiotics.

Certain properties of the bleomycin analogs deglycobleomycin A2 and decarbamoylbleomycin A2 have been characterized. In common with bleomycin A2, both deglycobleomycin A2 and decarbamoylbleomycin A2 were found to mediate DNA degradation in the presence of Fe(II) + O2. Both analogs were found to have essentially the same sequence selectivity for DNA strand scission as bleomycin A2 when a 5'-[23P]-end-labeled linear duplex DNA derived from SV40 DNA was employed as a substrate. Product analysis for the three analogs was carried out by assay for malondialdehyde (precursors) after digestion of calf thymus DNA, and also by hplc analysis of the digestion products formed from the dodecanucleotide d(CGCTTTAAAGCG). All three Fe(II) X bleomycin A2 analogs produced the same products, albeit not in the same relative amounts.

Base Sequence↗
PubMedDate not supplied

5-Alkylresorcinols from Hakea amplexicaulis that cleave DNA.

A dichloromethane extract of Hakea amplexicaulis was found to cause strand scission of phi X174 replicative form DNA in the presence of Cu(II). Bioassay-guided fractionation of this extract afforded five compounds capable of mediating DNA relaxation. Structure determination of the active principles indicated that they were 5-tridecylresorcinol (1), 5-pentadec-cis-8-enylresorcinol (2), 5-heptadeca-8,11-dienylresorcinol (3), 5-pentadecylresorcinol (4), and 5-heptadec-cis-8-enylresorcinol (5). As noted previously for compounds in this structural series, DNA cleavage was enhanced significantly by incubation under (alkaline) conditions known to promote oxygenation of the parent compounds on the aromatic nucleus.

Alkylation↗
PubMedDate not supplied

9-Octadecynoic acid: a novel DNA binding agent.

A novel bioassay was developed to permit the identification of cytotoxic natural principles that bind to DNA. A hexane extract of Schoepfia californica cytotoxic to cultured KB cells displayed much less cytotoxic potential when the culture medium contained exogenously added calf thymus DNA. Fractionation of the extract afforded a purified principle shown to be 9-octadecynoic acid, an 18-carbon, unbranched acetylenic fatty acid. 9-Octadecynoic acid had an apparent DNA dissociation constant of 1.8 mM; it inhibited topoisomerase I mediated DNA filter binding but did not inhibit the DNA topoisomerase I mediated relaxation of a supercoiled plasmid DNA. The fatty acid was weakly inhibitory to DNA polymerase alpha. 9-Octadecynoic acid possesses none of the structural characteristics of known DNA binding molecules and may bind to DNA by some novel mechanism.

Adenosine Triphosphate↗
PubMedDate not supplied

Inhibition of topoisomerase I function by nitidine and fagaronine.

The benzophenanthridine alkaloids nitidine and fagaronine were characterized as inhibitors of topoisomerase I function. In common with the antitumor agent camptothecin, both nitidine and fagaronine stabilized the covalent binary complex formed between calf thymus topoisomerase I and DNA. The effects of these compounds were readily apparent at 0.15-0.3 microM concentrations. Both nitidine and fagaronine inhibited the topoisomerase I-mediated relaxation of supercoiled pSP64 plasmid DNA more effectively than camptothecin; unlike camptothecin, both of these benzophenanthridine alkaloids also bound directly to and mediated the unwinding of B-form DNA. Nitidine and fagaronine were also studied in comparison with camptothecin to determine the sequence specificity of DNA breaks produced from a 32P-end-labeled duplex in the presence of topoisomerase I. All three compounds produced very similar cleavage patterns. The specificity of nitidine and fagaronine for inhibiting topoisomerase I function was studied by measuring the effects of the compounds on the unknotting of P4 DNA by calf thymus topoisomerase II. Moderate inhibition of topoisomerase II-mediated unknotting was obtained, but only in the presence of high (i.e., 40 microM) concentrations of nitidine and fagaronine. In comparison, doxorubicin inhibited topoisomerase II to the same extent as nitidine and fagaronine when it was employed at 2.5 microM concentration and was strongly inhibitory when employed at 10 microM concentration.

Alkaloids↗
PubMedDate not supplied

Inhibition of topoisomerase I function by coralyne and 5,6-dihydrocoralyne.

The antitumor agent coralyne and a number of structural analogues were found to be inhibitors of DNA topoisomerase I and were characterized biochemically. Several of these analogues stabilized the covalent binary complex formed between calf thymus topoisomerase I and pSP64 plasmid DNA; coralyne and 5,6-dihydrocoralyne had the greatest potency as inhibitors in this assay. In common with camptothecin, the effects of coralyne and 5,6-dihydrocoralyne were reversed in the presence of increasing salt concentration or temperature, consistent with the interpretation that both functioned mechanistically in a fashion analogous to camptothecin. The sequence specificity of DNA cleavage by coralyne and 5,6-dihydrocoralyne was also studied in comparison with camptothecin using a 471-bp DNA duplex as a substrate for topoisomerase I. Seven sites of cleavage were apparent, four of which were shared in common by coralyne, 5,6-dihydrocoralyne and camptothecin. Coralyne and 5,6-dihydrocoralyne produced cleavage at one sequence, 5'-TCTC decreases GTAA=3', that was not apparent in the presence of camptothecin; correspondingly, two cleavage bands appeared only when camptothecin was present. Coralyne and 5,6-dihydrocoralyne also inhibited topoisomerase I-mediated relaxation of supercoiled plasmid DNA. Coralyne was the most potent inhibitor of DNA relaxation; the effects of camptothecin and 5,6-dihydrocoralyne were roughly equal. At high concentrations, coralyne completely suppressed the formation of the topoisomerase I-DNA covalent binary complex.

Base Sequence↗
PubMedDate not supplied

Structurally altered substrates for DNA topoisomerase I. Effects of inclusion of a single 3'-deoxynucleotide within the scissile strand.

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.

Binding Sites↗