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Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides
This manuscript reports the molecular basis for double-stranded DNA (dsDNA) binding of hairpin polyamides incorporating a 5-alkyl thiazole (Nt) unit. Hairpin polyamides containing an N-terminal Nt unit induce higher melting stabilisation of target dsDNA sequences relative to an archetypical hairpin...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758887/ https://www.ncbi.nlm.nih.gov/pubmed/29194552 http://dx.doi.org/10.1093/nar/gkx1211 |
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author | Padroni, Giacomo Parkinson, John A Fox, Keith R Burley, Glenn A |
author_facet | Padroni, Giacomo Parkinson, John A Fox, Keith R Burley, Glenn A |
author_sort | Padroni, Giacomo |
collection | PubMed |
description | This manuscript reports the molecular basis for double-stranded DNA (dsDNA) binding of hairpin polyamides incorporating a 5-alkyl thiazole (Nt) unit. Hairpin polyamides containing an N-terminal Nt unit induce higher melting stabilisation of target dsDNA sequences relative to an archetypical hairpin polyamide incorporating an N-terminal imidazole (Im) unit. However, modification of the N-terminus from Im to Nt-building blocks results in an increase in dsDNA binding affinity but lower G-selectivity. A general G-selectivity trend is observed for Nt-containing polyamide analogues. G-selectivity increases as the steric bulk in the Nt 5-position increases. Solution-based NMR structural studies reveal differences in the modulation of the target DNA duplex of Nt-containing hairpin polyamides relative to the Im-containing archetype. A structural hallmark of an Nt polyamide•dsDNA complex is a more significant degree of major groove compression of the target dsDNA sequence relative to the Im-containing hairpin polyamide. |
format | Online Article Text |
id | pubmed-5758887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57588872018-01-16 Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides Padroni, Giacomo Parkinson, John A Fox, Keith R Burley, Glenn A Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry This manuscript reports the molecular basis for double-stranded DNA (dsDNA) binding of hairpin polyamides incorporating a 5-alkyl thiazole (Nt) unit. Hairpin polyamides containing an N-terminal Nt unit induce higher melting stabilisation of target dsDNA sequences relative to an archetypical hairpin polyamide incorporating an N-terminal imidazole (Im) unit. However, modification of the N-terminus from Im to Nt-building blocks results in an increase in dsDNA binding affinity but lower G-selectivity. A general G-selectivity trend is observed for Nt-containing polyamide analogues. G-selectivity increases as the steric bulk in the Nt 5-position increases. Solution-based NMR structural studies reveal differences in the modulation of the target DNA duplex of Nt-containing hairpin polyamides relative to the Im-containing archetype. A structural hallmark of an Nt polyamide•dsDNA complex is a more significant degree of major groove compression of the target dsDNA sequence relative to the Im-containing hairpin polyamide. Oxford University Press 2018-01-09 2017-11-29 /pmc/articles/PMC5758887/ /pubmed/29194552 http://dx.doi.org/10.1093/nar/gkx1211 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Chemical Biology and Nucleic Acid Chemistry Padroni, Giacomo Parkinson, John A Fox, Keith R Burley, Glenn A Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides |
title | Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides |
title_full | Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides |
title_fullStr | Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides |
title_full_unstemmed | Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides |
title_short | Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides |
title_sort | structural basis of dna duplex distortion induced by thiazole-containing hairpin polyamides |
topic | Chemical Biology and Nucleic Acid Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758887/ https://www.ncbi.nlm.nih.gov/pubmed/29194552 http://dx.doi.org/10.1093/nar/gkx1211 |
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