Issue February 2000

category image Volume 17
No. 4 (p 617-768)
February 2000
ISSN 0739-1102

Melting of Cross-Linked DNA IV. Methods for Computer Modeling of Total Influence on DNA Melting of Monofunctional Adducts, Intrastrand and Interstrand Cross-Links Formed by Molecules of an Antitumor Drug (p. 697-712)

A theoretical method is developed for calculation of melting curves of covalent complexes of DNA with antitumor drugs. The method takes into account all the types of chemical modifications of the double helix caused by platinum compounds and DNA alkylating agents: i) monofunctional adducts bound to one nucleotide; ii) intrastrand cross-links which appear due to bidentate binding of a drug molecule to two nucleotides that are included into the same DNA strand; iii) interstrand cross-links caused by bidentate binding of a molecule to two nucleotides of different strands. The developed calculation method takes into account the following double helix alterations at sites of chemical modifications: i) a change in stability of chemically modified base pairs and neighboring ones, that is caused by all the types of chemical modifications; ii) a change in the energy of boundaries between helical and melted regions at sites of chemical modification (local alteration of the factor of cooperativity of DNA melting), that is caused by all the types of chemical modifications, too; iii) a change in the loop entropy factor of melted regions that include interstrand cross-links; iv) the prohibition of divergence of DNA strands in completely melted DNA molecules, which is caused by interstrand cross-links only. General equations are derived, and three calculation methods are proposed to calculate DNA melting curves and the parameters that characterize the helix-coil transition.

Dmitri Y. Lando1*
Alexander S. Fridman1
Samvel G. Haroutiunian2
Albert S. Benight3
Philippe Collery4

1 Institute of Bioorganic Chemistry
Belarus National Academy of Sciences
Kuprevich St. 5/2
220141 Minsk, Belarus
2Chair of Molecular Physics
Department of Physics
Yerevan State University
375049 Yerevan, Armenia
3Department of Chemistry
(M/C 111)
Science and Engineering
South University of Illinois at Chicago
845 West Taylor Street
Room 4500
Chicago, Illinois 60607-7061, USA
4Research Institute on Metal Ions
45, rue Cognacq Jay
51092 Reims Cedex, France
*Lando@ns.iboch.ac.by

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