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In biochemistry, intercalation is the insertion of molecules between the planar bases of deoxyribonucleic acid (DNA). This process is used as a method for analyzing DNA and it is also the basis of certain kinds of poisoning.
Intercalation induces structural distortions. Left: unchanged DNA strand. Right: DNA strand intercalated at three locations (black areas).Ethidium intercalated between two adenine-thymine base pairs.
There are several ways molecules (in this case, also known as ligands) can interact with DNA. Ligands may interact with DNA by covalently binding, electrostatically binding, or intercalating.[1] Intercalation occurs when ligands of an appropriate size and chemical nature fit themselves in between base pairs of DNA. These ligands are mostly polycyclic, aromatic, and planar, and therefore often make good nucleic acid stains. Intensively studied DNA intercalators include berberine, ethidium bromide, proflavine, 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 ruthenium(II), because its complexes are very slow to decompose in the biological environment. Other metallic cations that have been used include rhodium(III) and iridium(III). Typical ligands attached to the metal ion are 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 ethidium bromide found in aqueous solution) unwinds DNA by about 26°, whereas proflavine unwinds it by about 17°. This unwinding causes the base pairs to separate, or "rise", creating an opening of about 0.34 nm (3.4 Å). This unwinding induces local structural changes to the DNA strand, such as lengthening of the DNA strand or twisting of the base pairs. These structural modifications can lead to functional changes, often to the inhibition of transcription and replication and DNA repair processes, which makes intercalators potent mutagens. For this reason, DNA intercalators are often carcinogenic, such as the exo (but not the endo) 8,9 epoxide of aflatoxin B1 and acridines such as proflavine or 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.
^Richards, A. D.; Rodgers, A. (2007). "Synthetic metallomolecules as agents for the control of DNA structure" (PDF). Chemical Society Reviews. 36 (3): 471–83. doi:10.1039/b609495c. PMID 17325786.
^Schatzschneider, Ulrich (2018). "Chapter 14. Metallointercalators and Metalloinsertors: Structural Requirements for DNA Recognition and Anticancer Activity". In Sigel, Astrid; Sigel, Helmut; Freisinger, Eva; Sigel, Roland K. O. (eds.). Metallo-Drugs: Development and Action of Anticancer Agents. Vol. 18. Berlin: de Gruyter GmbH. pp. 387–435. doi:10.1515/9783110470734-020. PMID 29394033. {{cite book}}: |journal= ignored (help)
^Lerman, L. S. (1961). "Structural considerations in the interaction of DNA and acridines" (PDF). Journal of Molecular Biology. 3 (1): 18–30. doi:10.1016/S0022-2836(61)80004-1. PMID 13761054.
^Luzzati, V.; Masson, F.; Lerman, L. S. (1961). "Interaction of DNA and proflavine: A small-angle x-ray scattering study". Journal of Molecular Biology. 3 (5): 634–9. doi:10.1016/S0022-2836(61)80026-0. PMID 14467543.
^Lerman, L. S. (1963). "The structure of the DNA-acridine complex". Proceedings of the National Academy of Sciences of the United States of America. 49 (1): 94–102. Bibcode:1963PNAS...49...94L. doi:10.1073/pnas.49.1.94. PMC300634. PMID 13929834.
April 10, 2024
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This article needs attention from an expert in Biology The specific problem is Need to be chunked into sections so that additional information can fit Need to have dsRNA mention See the talk page for details WikiProject Biology may be able to help recruit an expert November 2023 In biochemistry intercalation is the insertion of molecules between the planar bases of deoxyribonucleic acid DNA This process is used as a method for analyzing DNA and it is also the basis of certain kinds of poisoning Intercalation induces structural distortions Left unchanged DNA strand Right DNA strand intercalated at three locations black areas Ethidium intercalated between two adenine thymine base pairs There are several ways molecules in this case also known as ligands can interact with DNA Ligands may interact with DNA by covalently binding electrostatically binding or intercalating 1 Intercalation occurs when ligands of an appropriate size and chemical nature fit themselves in between base pairs of DNA These ligands are mostly polycyclic aromatic and planar and therefore often make good nucleic acid stains Intensively studied DNA intercalators include berberine ethidium bromide proflavine 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 ruthenium II because its complexes are very slow to decompose in the biological environment Other metallic cations that have been used include rhodium III and iridium III Typical ligands attached to the metal ion are 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 ethidium bromide found in aqueous solution unwinds DNA by about 26 whereas proflavine unwinds it by about 17 This unwinding causes the base pairs to separate or rise creating an opening of about 0 34 nm 3 4 A This unwinding induces local structural changes to the DNA strand such as lengthening of the DNA strand or twisting of the base pairs These structural modifications can lead to functional changes often to the inhibition of transcription and replication and DNA repair processes which makes intercalators potent mutagens For this reason DNA intercalators are often carcinogenic such as the exo but not the endo 8 9 epoxide of aflatoxin B1 and acridines such as proflavine or 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 editAnthracycline Intercalation chemistry Molecular tweezers Twisted intercalating nucleic acidReferences edit Richards A D Rodgers A 2007 Synthetic metallomolecules as agents for the control of DNA structure PDF Chemical Society Reviews 36 3 471 83 doi 10 1039 b609495c PMID 17325786 Schatzschneider Ulrich 2018 Chapter 14 Metallointercalators and Metalloinsertors Structural Requirements for DNA Recognition and Anticancer Activity In Sigel Astrid Sigel Helmut Freisinger Eva Sigel Roland K O eds Metallo Drugs Development and Action of Anticancer Agents Vol 18 Berlin de Gruyter GmbH pp 387 435 doi 10 1515 9783110470734 020 PMID 29394033 a href Template Cite book html title Template Cite book cite book a journal ignored help Lerman L S 1961 Structural considerations in the interaction of DNA and acridines PDF Journal of Molecular Biology 3 1 18 30 doi 10 1016 S0022 2836 61 80004 1 PMID 13761054 Luzzati V Masson F Lerman L S 1961 Interaction of DNA and proflavine A small angle x ray scattering study Journal of Molecular Biology 3 5 634 9 doi 10 1016 S0022 2836 61 80026 0 PMID 14467543 Lerman L S 1963 The structure of the DNA acridine complex Proceedings of the National Academy of Sciences of the United States of America 49 1 94 102 Bibcode 1963PNAS 49 94L doi 10 1073 pnas 49 1 94 PMC 300634 PMID 13929834 Retrieved from https en wikipedia org w index php title Intercalation biochemistry amp oldid 1187621799, wikipedia, wiki, book, books, library,
