DNA Minor Groove Binders-Inspired by Nature

Khalaf, Abedawn I.; Al-kadhimi, Ahmed A. H.; Ali, Jaafar H.

doi:10.17344/acsi.2016.2775

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…DNA groove binders could bind to the edges of DNA base pairs via reversible noncovalent interactions, 19 yet the conformation of DNA duplex was changeless. 20 To adapt with the shape of the minor groove, minor groove binders (MGBs) are often designed as isohelical and crescent-shaped molecules.…”

Section: Dna and Dna Bindersmentioning

confidence: 99%

Dual Inhibitors Targeting DNA and Histone Deacetylases

Chen

Xia

Hou

et al. 2020

Pharmaceutical Fronts

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AbstractHistone deacetylases (HDACs) regulate the acetylation status of histones and structural status of chromatin. The chromatin structure becomes relaxed after inhibition of HDAC, leading to DNA exposed to DNA disrupting agents, and eventually causing DNA dysfunction. Recently, more and more dual inhibitors targeting DNA and HDACs have been reported to be applied to cancer treatment. In this review, we describe the current status of dual inhibitors targeting DNA and HDACs, summarize their pharmacological characters, and predict their further trend in the field.

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Section: Dna and Dna Bindersmentioning

confidence: 99%

Dual Inhibitors Targeting DNA and Histone Deacetylases

Chen

Xia

Hou

et al. 2020

Pharmaceutical Fronts

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“…Several focused reviews on small molecule DNA binding agents have been published in recent years. A few have updated the progresses made in disease specific DNA binders [ 14 – 15 ] while others have included class specific or site-specific DNA binding agents [ 16 – 23 ]. A few others have covered nucleic acids binders in general [ 20 ] as well as an emerging therapeutic DNA target: the DNA G-quadruplex [ 24 ].…”

Section: Reviewmentioning

confidence: 99%

An overview of recent advances in duplex DNA recognition by small molecules

Bhaduri

Ranjan

Arya

2018

Beilstein J. Org. Chem.

107

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As the carrier of genetic information, the DNA double helix interacts with many natural ligands during the cell cycle, and is amenable to such intervention in diseases such as cancer biogenesis. Proteins bind DNA in a site-specific manner, not only distinguishing between the geometry of the major and minor grooves, but also by making close contacts with individual bases within the local helix architecture. Over the last four decades, much research has been reported on the development of small non-natural ligands as therapeutics to either block, or in some cases, mimic a DNA–protein interaction of interest. This review presents the latest findings in the pursuit of novel synthetic DNA binders. This article provides recent coverage of major strategies (such as groove recognition, intercalation and cross-linking) adopted in the duplex DNA recognition by small molecules, with an emphasis on major works of the past few years.

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“…An approach developed by Dervan et al over the last two decades for targeting CRPC is to inhibit the AR‐mediated transcription processes at the DNA level with direct antagonism of AR‐DNA binding using pyrrole‐imidazole containing polyamides. The idea was inspired by the function of the natural product distamycin A, a polyamide DNA minor groove binder, first isolated in 1962 from cultures of Streptomyces distallicus . Using the concept of differentiating nucleotide base pairs through specific positions of hydrogen bond donor or acceptor sites and through complementary geometrical flexibility to associate with DNA, these hairpin polyamides have evolved as a highly efficient means of specific recognition of DNA fragments .…”

Section: Hairpin Polyamide Antagonists Of Ar‐dna Bindingmentioning

confidence: 99%

Molecules targeting the androgen receptor (AR) signaling axis beyond the AR‐Ligand binding domain

Elshan¹,

Rettig

Jung³

2018

Medicinal Research Reviews

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Prostate cancer (PCa) is the second most common cause of cancer-related mortality in men in the United States. The androgen receptor (AR) and the physiological pathways it regulates are central to the initiation and progression of PCa. As a member of the nuclear steroid receptor family, it is a transcription factor with three distinct functional domains (ligand-binding domain [LBD], DNA-binding domain [DBD], and transactivation domain [TAD]) in its structure. All clinically approved drugs for PCa ultimately target the AR-LBD. Clinically active drugs that target the DBD and TAD have not yet been developed due to multiple factors. Despite these limitations, the last several years have seen a rise in the discovery of molecules that could successfully target these domains. This review aims to present and comprehensively discuss such molecules that affect AR signaling through direct or indirect interactions with the AR-TAD or the DBD. The compounds discussed here include hairpin polyamides, niclosamide, marine sponge-derived small molecules (eg, EPI compounds), mahanine, VPC compounds, JN compounds, and bromodomain and extraterminal domain inhibitors. We highlight the significant in vitro and in Med Res Rev. 2019;39:910-960. wileyonlinelibrary.com/journal/med 910 | -binding domain; LRP6, low-density lipoprotein receptor-related protein 6;MAPK, mitogen-activated protein kinase; mCRPC, metastatic castration-resistant prostate cancer; mTOR, mammalian target of rapamycin; NHR, nuclear hormone receptor; PARP, poly (ADP-ribose) polymerase; PCa, prostate cancer; PI3K, phosphatidylinositol-3 kinase; PPARγ, peroxisome-proliferatoractivated receptor-γ; PR, progesterone receptor; PSA, prostate-specific antigen; PTEN, phosphatase and tensin homolog; Py, N-methylpyrrole; RNAP2, RNA polymerase II; SAR, structure-activity relationship; SPOP, speckle-type POZ protein; STAT, signal transducer and activator of transcription; TAD, transactivation domain; TMPRSS, transmembrane protease serine 2. vivo data found for each compound and the apparent limitations and/or potential for further development of these agents as PCa therapies. K E Y W O R D S androgen receptor, androgen receptor degradation, androgen receptor signaling axis, androgen receptor DNA-binding domain, androgen receptor transactivation domain, castration-resistant prostate cancer, prostate cancer 1 | INTRODUCTION 1.1 | Physiologic role and regulation of the androgen receptor The androgen receptor (AR) is a ligand-activated DNA-binding transcription factor of 110 kDa molecular weight, which facilitates the expression of androgen-dependent gene products (Figure 1). 1,2 As a member of the steroid and nuclear hormone receptor (NHR) super family, it shares many structural and functional features with other receptors such as the glucocorticoid receptor (GR), estrogen receptor (ER), mineralocorticoid receptor, progesterone receptor (PR), and the vitamin D receptor. 3,4 The nuclear steroid receptors consist of three principal domains: (1) the carboxy-terminal ligandbinding domain (...

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DNA Minor Groove Binders-Inspired by Nature

Cited by 12 publications

References 40 publications

Dual Inhibitors Targeting DNA and Histone Deacetylases

Dual Inhibitors Targeting DNA and Histone Deacetylases

An overview of recent advances in duplex DNA recognition by small molecules

Molecules targeting the androgen receptor (AR) signaling axis beyond the AR‐Ligand binding domain

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