Biomedical subjects

L J Latimer

Publications and source records attributed to L J Latimer.

20 records · Page 2Linked to original sources

PubMedDate not supplied

A cooperative conformational change in duplex DNA induced by Zn2+ and other divalent metal ions.

Zn2+ and some other divalent metal ions bind to duplex DNA at pHs above 8 and cause a conformational change. This new structure does not bind ethidium, allowing the development of a rapid fluorescence assay. All duplex DNAs, regardless of sequence or G.C content, can form this structure. The rate of formation shows a strong dependence on temperature, pH, and Zn2+ concentration; at 20 degrees C, 1 mM Zn2+, and pH 8.6 the dismutation is half complete in 30 min. Addition of EDTA causes rapid reversion to 'B' DNA, showing that the new conformation retains two strands that are antiparallel. Unlike the ultraviolet or circular dichroism spectra, the nuclear magnetic resonance spectrum was informative since the imino protons of both A.T and G.C base pairs are lost upon addition of a stoichiometric amount of Zn2+. The pitch of the helix was estimated from gel electrophoresis of circular DNAs in the presence of Zn2+ and it contains at least 5% fewer base pairs per turn than 'B' DNA. The transformation is cooperative and shows hysteresis, suggesting that this is a distinct structure and not simply a minor variant of 'B' DNA. It is proposed to call this new structure 'M' DNA because of the intimate involvement of metal ions.

Circular Dichroism↗

PubMedDate not supplied

The binding of analogues of coralyne and related heterocyclics to DNA triplexes.

Coralyne has been shown previously to bind well to both T.A.T- and C.G.C(+)-containing triplexes. Derivatives of coralyne were prepared and their binding to poly(dT).poly(dA).poly(dT) and poly[d(TC)].poly[d(GA)].poly[d(C+T)] was assessed from thermal denaturation profiles. A tetraethoxy derivative showed only weak binding to both types of triplex. Analogues with extended 8-alkyl chains showed good binding to poly(dT).poly(dA).poly(dT), but the preference for triplex poly[d(TC)].poly[(GA)].poly[d(C+T)] was decreased compared with the duplex. Sanguinarine, a related alkaloid, bound well to poly(dT).poly(dA).poly(dT) but only weakly to the protonated triplex. It is hypothesized that the position of the protonated nitrogen ring is important for binding to poly[d(TC)].poly[d(GA)].poly[d(C+T)]. A series of other chromophores was studied and only those with a positive charge bound to triplexes. All of these bound well to poly(dT),poly(dA).poly(dT) but only weakly if at all to the duplex poly(dA).poly(dT). In contrast, most of them did not bind well to the triplex poly[d(TC)].poly[d(GA)].poly[d(C+T)] and those that did still showed a preference for duplex poly[d(TC)].poly[d(GA)]. In general, preference for triplex poly(dT).poly(dA).poly(dT) compared with the duplex is a common feature of intercalating drugs. On the other hand, specificity for protonated triplexes may be very difficult to achieve.

Alkaloids↗