Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.

Normal human genomic DNA (N-DNA) and mutated DNA (M-DNA) from K562 leukemic cells show different thermodynamic properties and binding affinities on interaction with anticancer drugs; adriamycin (ADR) and daunomycin (DNM). Isothermal calorimetric thermograms representing titration of ADR/DNM with N-D...

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Autores principales:	Debjani Ghosh, Subrata Kumar Dey, Chabita Saha
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d696a1ae2f614b448ebfe5c5442c6657
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spelling	oai:doaj.org-article:d696a1ae2f614b448ebfe5c5442c66572021-11-18T08:38:28ZMutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.1932-620310.1371/journal.pone.0084880https://doaj.org/article/d696a1ae2f614b448ebfe5c5442c66572014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24416304/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Normal human genomic DNA (N-DNA) and mutated DNA (M-DNA) from K562 leukemic cells show different thermodynamic properties and binding affinities on interaction with anticancer drugs; adriamycin (ADR) and daunomycin (DNM). Isothermal calorimetric thermograms representing titration of ADR/DNM with N-DNA and M-DNA on analysis best fitted with sequential model of four and three events respectively. From Raman spectroscopy it has been identified that M-DNA is partially transformed to A form owing to mutations and N-DNA on binding of drugs too undergoes transition to A form of DNA. A correlation of thermodynamic contribution and structural data reveal the presence of different binding events in drug and DNA interactions. These events are assumed to be representative of minor groove complexation, reorientation of the drug in the complex, DNA deformation to accommodate the drugs and finally intercalation. Dynamic light scattering and zeta potential data also support differences in structure and mode of binding of N and M DNA. This study highlights that mutations can manifest structural changes in DNA, which may influence the binding efficacy of the drugs. New generation of drugs can be designed which recognize the difference in DNA structure in the cancerous cells instead of their biochemical manifestation.Debjani GhoshSubrata Kumar DeyChabita SahaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84880 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Debjani Ghosh Subrata Kumar Dey Chabita Saha Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.
description	Normal human genomic DNA (N-DNA) and mutated DNA (M-DNA) from K562 leukemic cells show different thermodynamic properties and binding affinities on interaction with anticancer drugs; adriamycin (ADR) and daunomycin (DNM). Isothermal calorimetric thermograms representing titration of ADR/DNM with N-DNA and M-DNA on analysis best fitted with sequential model of four and three events respectively. From Raman spectroscopy it has been identified that M-DNA is partially transformed to A form owing to mutations and N-DNA on binding of drugs too undergoes transition to A form of DNA. A correlation of thermodynamic contribution and structural data reveal the presence of different binding events in drug and DNA interactions. These events are assumed to be representative of minor groove complexation, reorientation of the drug in the complex, DNA deformation to accommodate the drugs and finally intercalation. Dynamic light scattering and zeta potential data also support differences in structure and mode of binding of N and M DNA. This study highlights that mutations can manifest structural changes in DNA, which may influence the binding efficacy of the drugs. New generation of drugs can be designed which recognize the difference in DNA structure in the cancerous cells instead of their biochemical manifestation.
format	article
author	Debjani Ghosh Subrata Kumar Dey Chabita Saha
author_facet	Debjani Ghosh Subrata Kumar Dey Chabita Saha
author_sort	Debjani Ghosh
title	Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.
title_short	Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.
title_full	Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.
title_fullStr	Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.
title_full_unstemmed	Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.
title_sort	mutation induced conformational changes in genomic dna from cancerous k562 cells influence drug-dna binding modes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d696a1ae2f614b448ebfe5c5442c6657
work_keys_str_mv	AT debjanighosh mutationinducedconformationalchangesingenomicdnafromcancerousk562cellsinfluencedrugdnabindingmodes AT subratakumardey mutationinducedconformationalchangesingenomicdnafromcancerousk562cellsinfluencedrugdnabindingmodes AT chabitasaha mutationinducedconformationalchangesingenomicdnafromcancerousk562cellsinfluencedrugdnabindingmodes
_version_	1718421529728909312

Mutation induced conformational changes in genomic DNA from cancerous K562 cells influence drug-DNA binding modes.

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