Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region

DNA repair inhibitors are one of the latest additions to cancer chemotherapy. In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulati...
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Autor*in:	Sabrina Dallavalle [verfasserIn] Salvatore Princiotto [verfasserIn] Luce M. Mattio [verfasserIn] Roberto Artali [verfasserIn] Loana Musso [verfasserIn] Anna Aviñó [verfasserIn] Ramon Eritja [verfasserIn] Claudio Pisano [verfasserIn] Raimundo Gargallo [verfasserIn] Stefania Mazzini [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	NMR spectroscopy CD G-quadruplex molecular modeling PARP1 inhibitors fluorescence titration

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 22(2021), 16, p 8737
Übergeordnetes Werk:	volume:22 ; year:2021 ; number:16, p 8737

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms22168737

Katalog-ID:	DOAJ004893573

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callnumber-first	Q - Science
author	Sabrina Dallavalle
spellingShingle	Sabrina Dallavalle misc QH301-705.5 misc QD1-999 misc NMR spectroscopy misc CD misc G-quadruplex misc molecular modeling misc PARP1 inhibitors misc fluorescence titration misc Biology (General) misc Chemistry Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region
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topic_title	QH301-705.5 QD1-999 Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region NMR spectroscopy CD G-quadruplex molecular modeling PARP1 inhibitors fluorescence titration
topic	misc QH301-705.5 misc QD1-999 misc NMR spectroscopy misc CD misc G-quadruplex misc molecular modeling misc PARP1 inhibitors misc fluorescence titration misc Biology (General) misc Chemistry
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title	Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region
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title_full	Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region
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author_browse	Sabrina Dallavalle Salvatore Princiotto Luce M. Mattio Roberto Artali Loana Musso Anna Aviñó Ramon Eritja Claudio Pisano Raimundo Gargallo Stefania Mazzini
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title_sort	investigation of the complexes formed between parp1 inhibitors and parp1 g-quadruplex at the gene promoter region
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title_auth	Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region
abstract	DNA repair inhibitors are one of the latest additions to cancer chemotherapy. In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulating DNA repair are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. Several PARP1 inhibitors have been recently developed and approved for clinical treatments. We envisaged that PARP inhibition could be potentiated by simultaneously modulating the expression of PARP 1 and the enzyme activity, by a two-pronged strategy. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter has been recently identified. In this study, we explored the potential binding of clinically approved PARP1 inhibitors to the G-quadruplex structure found at the gene promoter region. The results obtained by NMR, CD, and fluorescence titration confirmed by molecular modeling demonstrated that two out the four PARP1 inhibitors studied are capable of forming defined complexes with the PARP1 G-quadruplex. These results open the possibility of exploring the development of better G-quadruplex binders that, in turn, may also inhibit the enzyme.
abstractGer	DNA repair inhibitors are one of the latest additions to cancer chemotherapy. In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulating DNA repair are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. Several PARP1 inhibitors have been recently developed and approved for clinical treatments. We envisaged that PARP inhibition could be potentiated by simultaneously modulating the expression of PARP 1 and the enzyme activity, by a two-pronged strategy. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter has been recently identified. In this study, we explored the potential binding of clinically approved PARP1 inhibitors to the G-quadruplex structure found at the gene promoter region. The results obtained by NMR, CD, and fluorescence titration confirmed by molecular modeling demonstrated that two out the four PARP1 inhibitors studied are capable of forming defined complexes with the PARP1 G-quadruplex. These results open the possibility of exploring the development of better G-quadruplex binders that, in turn, may also inhibit the enzyme.
abstract_unstemmed	DNA repair inhibitors are one of the latest additions to cancer chemotherapy. In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulating DNA repair are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. Several PARP1 inhibitors have been recently developed and approved for clinical treatments. We envisaged that PARP inhibition could be potentiated by simultaneously modulating the expression of PARP 1 and the enzyme activity, by a two-pronged strategy. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter has been recently identified. In this study, we explored the potential binding of clinically approved PARP1 inhibitors to the G-quadruplex structure found at the gene promoter region. The results obtained by NMR, CD, and fluorescence titration confirmed by molecular modeling demonstrated that two out the four PARP1 inhibitors studied are capable of forming defined complexes with the PARP1 G-quadruplex. These results open the possibility of exploring the development of better G-quadruplex binders that, in turn, may also inhibit the enzyme.
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title_short	Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region
url	https://doi.org/10.3390/ijms22168737 https://doaj.org/article/54dcbe5c6cb040e1b50345aa45e43603 https://www.mdpi.com/1422-0067/22/16/8737 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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author2	Salvatore Princiotto Luce M. Mattio Roberto Artali Loana Musso Anna Aviñó Ramon Eritja Claudio Pisano Raimundo Gargallo Stefania Mazzini
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up_date	2024-07-04T01:33:34.107Z
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In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulating DNA repair are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. Several PARP1 inhibitors have been recently developed and approved for clinical treatments. We envisaged that PARP inhibition could be potentiated by simultaneously modulating the expression of PARP 1 and the enzyme activity, by a two-pronged strategy. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter has been recently identified. In this study, we explored the potential binding of clinically approved PARP1 inhibitors to the G-quadruplex structure found at the gene promoter region. The results obtained by NMR, CD, and fluorescence titration confirmed by molecular modeling demonstrated that two out the four PARP1 inhibitors studied are capable of forming defined complexes with the PARP1 G-quadruplex. 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Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region

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