Document Detail

Inhibition of the thermally driven B to Z transition by intercalating drugs.
MedLine Citation:
PMID:  3828287     Owner:  NLM     Status:  MEDLINE    
Poly(dG-m5dC) in phosphate buffer containing 50 mM NaCl and Mg2+ will undergo a reversible thermally driven conversion from the B to the left-handed Z conformation. The temperature at the midpoint of the thermally driven B to Z transition (denoted Tz) is dependent upon the total Mg2+ concentration, with [d(1/Tz)]/(d ln [Mg]) = 0.0134 K-1. The Mg2+ concentration at the midpoint of the equilibrium B to Z transition curve, denoted [Mg]1/2, is dependent on temperature, with (d ln [Mg]1/2)/(d ln T) = -1.02. Binding of the anticancer drug daunomycin to the polymer results in a pronounced increase in Tz, dependent on the molar ratio of added drug. Tz is increased by 71.9 degrees C with nearly saturating amounts of drug bound. Transition profiles are biphasic at less than saturating amounts of bound drug. By experiments monitoring such biphasic curves at a visible wavelength sensitive to the binding of daunomycin, it may be demonstrated that no drug is released until the later phase of the transition. These results are analogous to the effects of intercalating drugs on the thermal denaturation of DNA and indicate that drug molecules preferentially interact with B-form DNA and are redistributed to regions in the B conformation over the course of the transition. Comparative studies show that some intercalators stabilize right-handed DNA more effectively than others. At similar initial binding ratios, the following order, from most to least effective, was experimentally observed: actinomycin greater than daunomycin greater than ethidium greater than proflavin.
J B Chaires
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  25     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1986 Dec 
Date Detail:
Created Date:  1987-05-20     Completed Date:  1987-05-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  8436-9     Citation Subset:  IM    
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MeSH Terms
Intercalating Agents*
Nucleic Acid Conformation*
Grant Support
Reg. No./Substance:
0/Intercalating Agents; 0/Polydeoxyribonucleotides; 51853-63-5/poly(dG-m(5)dC).poly(dG-m(5)dC); 7439-95-4/Magnesium; 9007-49-2/DNA
Erratum In:
Biochemistry 1987 Mar 24;26(6):1794

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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