Intercalation (biochemistry)

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Intercalation induces structural distortions. Left: unchanged DNA strand. Right: DNA strand intercalated at three locations (black areas).

In

deoxyribonucleic acid
(DNA). This process is used as a method for analyzing DNA and it is also the basis of certain kinds of poisoning.

Ethidium intercalated between two adenine-thymine base pairs.

There are several ways molecules (in this case, also known as

daunomycin, doxorubicin, and thalidomide. DNA intercalators are used in chemotherapeutic treatment to inhibit DNA replication in rapidly growing cancer cells. Examples include doxorubicin (adriamycin) and daunorubicin (both of which are used in treatment of Hodgkin's lymphoma), and dactinomycin
(used in Wilm's tumour, Ewing's Sarcoma, rhabdomyosarcoma).

Metallointercalators are complexes of a metal cation with polycyclic aromatic ligands. The most commonly used metal ion is

dipyridine and terpyridine whose planar structure is ideal for intercalation.[2]

In order for an intercalator to fit between base pairs, the DNA must dynamically open a space between its base pairs by unwinding. The degree of unwinding varies depending on the intercalator; for example, ethidium cation (the ionic form of

quinacrine
.

Intercalation as a mechanism of interaction between cationic, planar, polycyclic aromatic systems of the correct size (on the order of a base pair) was first proposed by Leonard Lerman in 1961.[3][4][5] One proposed mechanism of intercalation is as follows: In aqueous isotonic solution, the cationic intercalator is attracted electrostatically to the surface of the polyanionic DNA. The ligand displaces a sodium and/or magnesium cation present in the "condensation cloud" of such cations that surrounds DNA (to partially balance the sum of the negative charges carried by each phosphate oxygen), thus forming a weak electrostatic association with the outer surface of DNA. From this position, the ligand diffuses along the surface of the DNA and may slide into the hydrophobic environment found between two base pairs that may transiently "open" to form an intercalation site, allowing the ethidium to move away from the hydrophilic (aqueous) environment surrounding the DNA and into the intercalation site. The base pairs transiently form such openings due to energy absorbed during collisions with solvent molecules.

See also

References