14 research outputs found

    More pronounced salt dependence and higher reactivity for platination of the hairpin r(CGCGUUGUUCGCG) compared with d(CGCGTTGTTCGCG)

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    The DNA interference pathways exhibited by cisplatin and related anticancer active metal complexes have been extensively studied. Much less is known to what extent RNA interaction pathways may operate in parallel, and perhaps contribute to both antineoplastic activity and toxicity. The present study was designed with the aim of comparing the reactivity of two model systems comprising RNA and DNA hairpins, r(CGCGUUGUUCGCG) and d(CGC GTTGTTCGCG), towards a series of platinum(II) complexes. Three platinum complexes were used as metallation reagents; cis-[ptCl(NH3)(2)(OH2)](+) (1), cis-[PtCl(NH3)(C-C6H11NH2)(OH2)](+) (2), and trans[PtCl(NH3)(quinoline)(OH2)](+) (3). The reaction kinetics were studied at pH 6.0, 25 degrees C, and 1.0 mM < 1: 500 mM. For both types of nucleic acid targets, compound 3 was found to react about 1 order of magnitude more rapidly than compounds 1 and 2. Further, all platinum compounds exhibited a more pronounced salt dependence for the interaction with r(CGCGUUGUUCGCG). Chemical and enzymatic cleavage studies revealed similar interaction patterns with r(CGCGUUGUUCGCG) after long exposure times to 1 and 2. A substantial decrease of cleavage intensity was found at residues G4 and G7, indicative of bifunctional adduct formation. Circular dichroism studies showed that platinum adduct formation leads to a structural change of the ribonucleic acid. Thermal denaturation studies revealed platination to cause a decrease of the RNA melting temperatures by 5-10 degrees C. Our observations therefore suggest that RNA is a kinetically competitive target to DNA. Furthermore, platination causes destabilization of RNA structural elements, which may lead to deleterious intracellular effects on biologically relevant RNA targets

    Comparative genetic structure of two co-occurring tree species, Maclura pomifera (Moraceae) and Gleditsia triacanthos (Leguminosae)

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    Maclura pomifera, an autotetraploid, and Gleditsia triacanthos, a diploid, are ecologically similar dioecious tree species that often co-occur in early successional habitats throughout the mid-western United States. We studied levels of genetic diversity and patterns of genetic structure for four polymorphic enzyme loci of M. pomifera and 16 polymorphic enzyme loci of G. triacanthos from a single population in eastern Kansas. Levels of expected heterozygosity were high for both species, averaging 0.725 for M. pomifera and 0.366 for G. triacanthos. Although genotypes for nearly all G. triacanthos loci were in Hardy-Weinberg frequencies, three of four M. pomifera loci deviated from equilibrium expectations. Two aspects of genetic structure were explored. First, the extent of clonal growth was estimated by comparing genotypes of stems within 50 G. triacanthos and 32 M. pomifera clumps. The great majority of clumps contained more than one genotype, and in many clumps, all stems were genetically unique. Secondly, as revealed by spatial autocorrelation analyses, genetic substructure was very local for both species, with significant positive autocorrelation occurring only within clumps of individuals or among near neighbours. We argue that this pattern of spatial structure for both species results from extremely local seed dispersal and establishment of individuals from the same multiseeded fruit
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