Biomedical subjects

E T Zuo

Publications and source records attributed to E T Zuo.

4 recordsLinked to original sources

PubMed1990

Effect of base-pair sequence on the conformations and thermally induced transitions in oligodeoxyribonucleotides containing only AT base pairs.

Tm curves, CD spectra, and kinetics results of the self-complementary DNA dodecamers d(A6T6), d(A3T3A3T3), d(A2T2A2T2A2T2), d(ATATATATATAT), and d(T6A6) demonstrate that the thermal transitions of these oligomers at low salt concentration involve a hairpin intermediate. At high salt concentrations (greater than 0.1 M Na+) only a duplex to denatured-strand transition appears to occur. The temperature and salt-concentration regions of the transitions are very sequence dependent. Alternating-type AT sequences have a lower duplex stability and a greater tendency to form hairpins than sequences containing more nonalternating AT base pairs. Of the two nonalternating sequences, d(T6A6) is significantly less stable than d(A6T6). Both oligomers have CD curves that are very similar to the unusual CD spectrum of poly(dA).poly(dT). The Raman spectra of these two oligomers are also quite similar, but at low temperature, small intensity differences in two backbone modes and three nucleoside vibrations are obtained. The hairpin to duplex transition for the AT dodecamers was examined by salt-jump kinetics measurements. The transition is faster than transitions for palindromic-sequence oligomers containing terminal GC base pairs. Stopped-flow kinetics studies indicate that the transition is second order and has a relatively low activation energy. The reaction rate increases with increasing ionic strength. These results are consistent with a three-step mechanism for the hairpin to duplex reaction: (i) fraying of the hairpin oligomers' terminal base pairs, (ii) a rate-determining bimolecular step involving formation of a cruciform-type intermediate from two hairpin oligomers with open terminal base pairs, and (iii) base-pair migration and formation in the intermediate to give the duplex.

Adenine↗

PubMed1988

Unusual duplex formation in purine rich oligodeoxyribonucleotides.

The purine rich oligodeoxyribonucleotides 1C, d(ATGACGGAATA) and 2C, d(ATGAGCGAATA) alone exhibit highly cooperative melting transitions. Analysis of the concentration dependence of melting, and electrophoretic studies indicate that these oligomers can form an unusual purine rich offset double helix. The unusual duplex is predicted to contain four A.T, two G.C, and four G.A mismatch base pairs as well as a single A base stacked on the 3' end of each chain of the helix. Other possible models for the duplex are unlikely because they are predicted to contain many base pairs of low stability. Changing the central sequence to CGG or GGG should destabilize the duplex and this is observed. The unusual duplex of 2C is more stable than the duplex of 1C indicating that the stability of G.A base pairs is quite sensitive to the surrounding sequence. Addition of 1C and 2C to their complementary pyrimidine strands results in normal duplexes of similar stability. We feel that the unusual duplexes are significantly stabilized by the intrinsic stacking tendency of purine bases.

Base Composition↗

PubMed1988

Characteristics of the interaction of anthrapyrazole anticancer agents with deoxyribonucleic acids: structural requirements for DNA binding, intercalation, and photosensitization.

The binding constants for interaction of several novel anthra[1,9-cd]pyrazol-6(2H)-ones (anthrapyrazoles) with DNA have been determined by an ethidium displacement method. The apparent binding constants range from less than 2 X 10(6) to 2.7 X 10(8) M-1. The binding is influenced not only by the nature of the side chains but also by the number and position of hydroxyl groups on the chromophore. Unwinding angles, determined by a topoisomerase I assay, ranged from 0 degrees to 29.2 degrees. The deshydroxy compound 1 gave the highest unwinding angle, and both substitution of hydroxyl groups in the chromophore and alterations in the side chains decrease the unwinding angle, consistent with a decreased or partial intercalation. Representative anthrapyrazoles cause an increase in sonicated DNA viscosity as expected for intercalators. Spectrophotometric examination of the binding of compound 1 to DNAs of different base composition show that the apparent binding to GC is approximately 3 times that of AT, a result which was paralleled by thermal denaturation studies. Certain of the anthrapyrazoles exhibit marked visible light photosensitization and induce DNA single-strand breakage upon illumination in the presence of NADH. The essential structural requirement for photosensitizing properties with these agents was the absence of hydroxyl groups in the chromophore. By employing 32P-labeled DNA of known sequence, it was possible to examine the anthrapyrazole 1-photosensitized cleavage of DNA at the individual base level employing denaturing polyacrylamide sequencing gels. Smooth sequence neutral photosensitized cleavage of DNA is observed analogous to hydroxyl radical "footprinting."

Anthraquinones↗

PubMed1987

Sequence dependent electrophoretic mobilities and melting temperatures for A-T containing oligodeoxyribonucleotides.

The electrophoretic mobilities and thermal melting properties of self complementary A-T containing dodecamer oligodeoxyribonucleotides have been investigated as a function of solution conditions. The oligomers contained tracts of nonalternating A-T base pairs of 2 (d(A2T2)3), 3 (d(A3T3)2), and 6 (d(A6T6] as well as the fully alternating (d(A-T)6) sequence. The melting temperature increased with the length of the nonalternating sequence and was approximately 12 degrees C higher in the d(A6T6) sequence than in the alternating oligomer. Under denaturing conditions all oligomers had the same electrophoretic mobility on acrylamide gels. Under conditions which favor duplex formation, the oligomers exhibited significant sequence dependent mobility differences. The mobilities of two oligomers, d(A-T)6 and d(A6-T6), were approximately equal and were less than those of the other oligonucleotides. The greatest mobility was observed for d(A2T2)3. These results are best explained by a model which requires bending at a junction of two or more continuous A or T bases with another sequence.

Adenine↗