Cell penetrating thiazole peptides inhibit c-MYC expression via site-specific targeting of c-MYC G-quadruplex

Dutta, Debasish; Debnath, Manish; Müller, Diana; Paul, Rakesh; Das, Tania; Bessi, Irene; Schwalbe, Harald; Dash, Jyotirmayee

doi:10.1093/nar/gky385

Cited by 84 publications

(74 citation statements)

References 51 publications

(40 reference statements)

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“…Polyamides based on 2 and 3 repeating units of 2-aminothiazole-4-carboxylic acid were synthetized [69] and proved to bind selectively to c-MYC quadruplex over other G-quadruplex and duplex DNA and therefore inhibiting c-MYC oncogene transcription. Antiproliferative activity of the tripeptide was found in HeLa cells, caused by apoptotic pathway.…”

Section: Linear Peptidesmentioning

confidence: 99%

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Ramos-Inza¹,

Aydillo²,

Sanmartín³

et al. 2020

Heterocycles - Synthesis and Biological Activities

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Currently, cancer is one of the major health problems of the human population and prominent cause of death. Thiazole ring has demonstrated many pharmacological activities including anticancer. This scaffold has been found alone or incorporated into the diversity of therapeutic active agents such as tiazofurin, dasatinib, and bleomycin, which are well-known antineoplastic drugs. Recently, most of the compounds isolated from natural sources containing thiazole moiety exhibit notable cytotoxicities and present antitumor potential. In this context, several structural changes have been made in the original structure, such as the incorporation of different substituents or the fusion with other carbo-and heterocycles, in order to increase the antitumoral potency. Related to mechanism of action of these derivatives, some of them act through kinase modulation, polymerization inhibition of microtubule, pro-matrix metalloproteinase activation, signal transducer activation of transcription 3, histone deacetylase inhibition, etc.

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Section: Linear Peptidesmentioning

confidence: 99%

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Ramos-Inza¹,

Aydillo²,

Sanmartín³

et al. 2020

Heterocycles - Synthesis and Biological Activities

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show abstract

“…resolved for transcription to occur. Compounds like enniantin-B, TH3, and APTO-253 that stabilize this structure decrease MYC transcription (44,45). Furthermore, efficient MYC gene transcription needs docking of BRD proteins and other co-activating molecules, including IKZF, NME2, and CDK9 at the promoter.…”

Section: Thematic Minireview: Myc-odc Axis In Cancermentioning

confidence: 99%

Polyamine synthesis as a target of MYC oncogenes

Bachmann

Geerts

2018

Journal of Biological Chemistry

106

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Edited by Ronald C. Wek This paper is in recognition of the 100th birthday of Dr. Herbert Tabor, a true pioneer in the polyamine field for over 70 years, who served as the editor-in-chief of the Journal of Biological Chemistry from 1971 to 2010. We review current knowledge of MYC proteins (c-MYC, MYCN, and MYCL) and focus on ornithine decarboxylase 1 (ODC1), an important bona fide gene target of MYC, which encodes the sentinel, rate-limiting enzyme in polyamine biosynthesis. Although notable advances have been made in designing inhibitors against the "undruggable" MYCs, their downstream targets and pathways are currently the main avenue for therapeutic anticancer interventions. To this end, the MYC-ODC axis presents an attractive target for managing cancers such as neuroblastoma, a pediatric malignancy in which MYCN gene amplification correlates with poor prognosis and high-risk disease. ODC and polyamine levels are often up-regulated and contribute to tumor hyperproliferation, especially of MYC-driven cancers. We therefore had proposed to repurpose ␣-difluoromethylornithine (DFMO), an FDA-approved, orally available ODC inhibitor, for management of neuroblastoma, and this intervention is now being pursued in several clinical trials. We discuss the regulation of ODC and polyamines, which besides their well-known interactions with DNA and tRNA/rRNA, are involved in regulating RNA transcription and translation, ribosome function, proteasomal degradation, the circadian clock, and immunity, events that are also controlled by MYC proteins.

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“…There have been efforts to develop ligands that will bind specifically to each G4 structure. Thiazole peptides were developed and tested for specific c-MYC G4 binding [64]. These experiments also showed that the ligand binds to c-MYC's G4 in slow exchange on the NMR timescale.…”

Section: G4-ligand Interactionmentioning

confidence: 99%

Dynamics Studies of DNA with Non-canonical Structure Using NMR Spectroscopy

Kim

Park

Lee

2020

IJMS

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The non-canonical structures of nucleic acids are essential for their diverse functions during various biological processes. These non-canonical structures can undergo conformational exchange among multiple structural states. Data on their dynamics can illustrate conformational transitions that play important roles in folding, stability, and biological function. Here, we discuss several examples of the non-canonical structures of DNA focusing on their dynamic characterization by NMR spectroscopy: (1) G-quadruplex structures and their complexes with target proteins; (2) i-motif structures and their complexes with proteins; (3) triplex structures; (4) left-handed Z-DNAs and their complexes with various Z-DNA binding proteins. This review provides insight into how the dynamic features of non-canonical DNA structures contribute to essential biological processes.

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Cell penetrating thiazole peptides inhibit c-MYC expression via site-specific targeting of c-MYC G-quadruplex

Cited by 84 publications

References 51 publications

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Polyamine synthesis as a target of MYC oncogenes

Dynamics Studies of DNA with Non-canonical Structure Using NMR Spectroscopy

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