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Biomedical subjects

M Zhong

Publications and source records attributed to M Zhong.

95 records · Page 6Linked to original sources
PubMed1993

Effect of T-T base mismatches on three-arm DNA junctions.

In contrast to four-arm immobile DNA junctions, three-arm DNA junctions have unique structural and dynamic properties consistent with lack of a single dominant conformation. The effect of T-T base mismatches at the branch in a three-arm model junction has been investigated using a combination of electrophoretic mobility measurements, chemical footprinting experiments, and thermodynamic studies. The results indicate that three-arm junctions are only slightly destabilized by a mismatch flanking the branch, relative to four-arm junctions. The effect of a mismatch varies with the sequence and position of the site of the mismatch. Since a three-arm junction with two mismatches flanking the branch is as stable as two junctions each with a single mismatch, the stability of three-arm junctions is not determined by stacking interactions at the branch in a simple way. The properties of three-arm junctions with one or two mismatches are consistent with a picture in which the conformation is the result of several substrates in which base pairs flanking the branch are transiently open, allowing bases to interact with the remaining duplexes.

Base Sequence↗
PubMed1993

Conformation and thermodynamics of DNA "necks". Models for three-arm branch formation in a duplex.

The properties of three-arm DNA junctions differ from those of four-arm junctions in several respects. Most apparently, bases flanking the branch are reactive to single strand specific agents in three-arm junctions but not four-arm junctions. To determine the basis for this, we have designed and synthesized a series of complexes in which a short duplex, a neck, progressively extends from a parent 16-mer DNA duplex. These structure allow us to investigate how a three-arm branch forms, and how its properties change as the neck extends. Comparison of the properties of a nicked duplex with those of the neck structures using native gel electrophoresis with reporter arms attached reveals progressively greater geometrical perturbation of the complexes as the number of base-pairs in the neck increases. Footprinting by single-strand specific reagents indicates that the reactivity to single-strand reagents near the branch occurs when only a single pair is possible. The branch in each neck interacts tightly with ethidium, as does a nick in the same duplex. The thermodynamics of neck formation have been evaluated by calorimetry and from the concentration dependence of absorbance temperature profiles. Each neck complex is destabilized with respect to duplex DNA or a nicked duplex, and has a lower enthalpy of formation despite the increased number of base-pairs present. A model is proposed to account for these properties in which the bases in the pair adjacent to the duplex interact directly with the duplex, via transient insertion.

Base Sequence↗
PubMed1992

T-T base mismatches enhance drug binding at the branch site in a four-arm DNA junction.

Base mismatches--non Watson-Crick pairing between bases--can arise in duplex DNA as a consequence of mutational events or by recombination. In a duplex, the sequence of the two bases involved, and those flanking the site of mismatch, determines the local structure and extent of destabilization of the helix. Base mismatches can arise also in recombination of nonhomologous strands, and their occurrence in Holliday recombination intermediates can influence the outcome of general or specialized recombination events. We have previously reported that the branch site in a DNA junction can interact selectively with a variety of ligands. Here we describe the thermodynamics of junctions containing T-T mismatches flanking the branch and show that these structures bind methidium and other intercalators with higher affinity than junctions lacking mismatches.

Base Composition↗
PubMed1992

Use of fluoroquinolones for prophylaxis of murine Pneumocystis carinii pneumonia.

We compared the prophylactic activities of six fluoroquinolones against Pneumocystis carinii pneumonia in immunosuppressed rats. Pefloxacin was the only agent which was as effective as the reference drug trimethoprim-sulfamethoxazole. Clinical trials with pefloxacin in patients at risk for P. carinii pneumonia appear to be justified.

4-Quinolones↗