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Biomedical subjects

T W Plumbridge

Publications and source records attributed to T W Plumbridge.

6 recordsLinked to original sources
PubMed1979

The interaction of adriamycin and adriamycin analogues with nucleic acids in the B and A conformations.

The reinforced intercalative binding to DNA typical of adriamycin and daunomycin can still occur if there is epimerisation at C4' or if the O-methyl group is lost or if the 9-substituents are deleted or if the 4'-hydroxyl group is lost. In the latter two cases however, there is a reduction in affinity for the DNA, supporting the suggested role of the 9-hydroxyl and 4'-hydroxyl groups in secondary stabilization of the complex. Epimerisation at C-1' or at C-3' alters but does not abolish the intercalative mode of binding to DNA whereas epimerisation at C-7 precludes intercalation of the chromophore into the helix of DNA. In contrast to the interaction with the B-form found in DNA, the parent drugs do not intercalate into nucleic acids possessing the A-conformation and none of the above-mentioned structural changes will allow intercalation into A-form nucleic acids.

DNA↗
PubMed1978

Problems associated with analysis and interpretation of small molecule/macromolecule binding data.

In the analysis of binding data, arbitrary transformations such as the Scatchard plot, may give misleading estimates of the binding parameters. The statistically correct approach is to determine values of K and n by non-linear regression of the actual dependent variable against the actual independent variable. In the case of the spectrophotometric titration method the dependent variable is the absorbance and the independent variable is the composition of the drug/macromolecule mixture. The method relies on an accurate estimate of the extinction coefficient of the bound drug and this is best treated as a parameter to be estimated in the regression analysis. In testing models by data fits alone it is emphasized that whilst a model may be rejected if it does not fit the data, a good fit does not ensure uniquieness and confirmatory, independent evidence must be sought.

DNA↗
PubMed1977

Spectrophotometric and fluorescence polarization studies of the binding of ethidium, daunomycin and mepacrine to DNA and to poly(I-C).

The changes in the visible absorption spectrum and the degree of fluorescence polarization of daunomycin and mepacrine on binding to DNA have been compared with those shown by the archetypical intercalating agent ethidium. The changes are qualitatively similar for the three drugs, namely a bathochromic shift and hypochromicity (giving an isosbestic point) and an increase in polarization of fluorescence when irradiated with polarized light. These effects are typical of intercalation. The effect of changing the nucleic acid conformation has been investigated by repeating the studies with poly(I-C) (a nucleic acid in the A conformation). Upon interaction with poly(I-C) only ethidium shows effects typical of intercalation, neither daunomycin nor mepacrine intercalates into poly(I-C) helix.

Chemical Phenomena↗