Developing new chemical tools for DNA methyltransferase 1 (DNMT 1): A small-molecule activity-based probe and novel tetrazole-containing inhibitors

Zhu, Biwei; Ge, Jingyan; Yao, Shao Q.

doi:10.1016/j.bmc.2015.03.006

Cited by 26 publications

(26 citation statements)

References 48 publications

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“…Zhu et al . developed chemical tools based on maleimide‐based DNMT inhibitors . The authors added to the maleimide inhibitor moiety an alkyne function to be used as a handle.…”

Section: Chemical Biology Tools To Better Understand Epigenetics In Pmentioning

confidence: 99%

Natural Products and Chemical Biology Tools: Alternatives to Target Epigenetic Mechanisms in Cancers

Lascano

Lopez

Arimondo

2018

The Chemical Record

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DNA methylation and histone acetylation are widely studied epigenetic modifications. They are involved in numerous pathologies such as cancer, neurological disease, inflammation, obesity, etc. Since the discovery of the epigenome, numerous compounds have been developed to reverse DNA methylation and histone acetylation aberrant profile in diseases. Among them several were inspired by Nature and have a great interest as therapeutic molecules. In the quest of finding new ways to target epigenetic mechanisms, the use of chemical tools is a powerful strategy to better understand epigenetic mechanisms in biological systems. In this review we will present natural products reported as DNMT or HDAC inhibitors for anticancer treatments. We will then discuss the use of chemical tools that have been used in order to explore the epigenome.

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“…Zhu et al . developed chemical tools based on maleimide‐based DNMT inhibitors . The authors added to the maleimide inhibitor moiety an alkyne function to be used as a handle.…”

Section: Chemical Biology Tools To Better Understand Epigenetics In Pmentioning

confidence: 99%

Natural Products and Chemical Biology Tools: Alternatives to Target Epigenetic Mechanisms in Cancers

Lascano

Lopez

Arimondo

2018

The Chemical Record

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“…22-24 Similar strategies have begun to emerge for MTs, where, for instance, SAM analogues that transfer an alkyne have been used to identify MT substrates. 25 Likewise, first-generation photoreactive- and fluorescent/biotin-coupled probes based on the general MT inhibitors DzNep 26 and SAH, 27,28 as well as more selective DNMT 29 and DOT1L 30 inhibitors, have been introduced with the potential to enrich and identify MTs from native proteomes. While these previous efforts have succeeded in labeling and enriching a handful of MTs, the broader potential for chemical proteomic methods to target endogenous human MTs in complex biological systems with good scope and selectivity remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Chemical Proteomic Profiling of Human Methyltransferases

et al. 2016

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Methylation is a fundamental mechanism used in Nature to modify the structure and function of biomolecules, including proteins, DNA, RNA, and metabolites. Methyl groups are predominantly installed into biomolecules by a large and diverse class of S-adenosyl methionine (SAM)-dependent methyltransferases (MTs), of which there are ~200 known or putative members in the human proteome. Deregulated MT activity contributes to numerous diseases, including cancer, and several MT inhibitors are in clinical development. Nonetheless, a large fraction of the human MT family remains poorly characterized, underscoring the need for new technologies to characterize MTs and their inhibitors in native biological systems. Here, we describe a suite of S-adenosyl homocysteine (SAH) photoreactive probes and their application in chemical proteomic experiments to profile and enrich a large number of MTs (> 50) from human cancer cell lysates with remarkable specificity over other classes of proteins. We further demonstrate that the SAH probes can enrich MT-associated proteins and be used to screen for and assess the selectivity of MT inhibitors, leading to the discovery of a covalent inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme implicated in cancer and metabolic disorders. The chemical proteomics probes and methods for their utilization reported herein should prove of value for the functional characterization of MTs, MT complexes, and MT inhibitors in mammalian biology and disease.

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“…This scaffold has recently acquired increasing attention from the medicinal chemistry community. For example, this substitution pattern has recently appeared in Breast Cancer Resistance Protein inhibitors 6 , DNA methyltransferases 1 inhibitors 7 , α 4 β 2 α 5 nicotinic acetylcholine receptors modulators 8 , FAAH inhibitors 9 and MDR1 inhibitors 10 . In addition to Lippmann’s and Ito’s synthetic methods, Han and co-workers reported the synthesis of 2-aryl-5-substituted tetrazoles through the coupling of 5-substituted tetrazoles with arylboronic acids in the presence of copper(II) 11 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2-aryl-2H-tetrazoles via a regioselective [3+2] cycloaddition reaction

Patouret

Kamenecka

2016

Tetrahedron Letters

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Developing new chemical tools for DNA methyltransferase 1 (DNMT 1): A small-molecule activity-based probe and novel tetrazole-containing inhibitors

Cited by 26 publications

References 48 publications

Natural Products and Chemical Biology Tools: Alternatives to Target Epigenetic Mechanisms in Cancers

Natural Products and Chemical Biology Tools: Alternatives to Target Epigenetic Mechanisms in Cancers

Chemical Proteomic Profiling of Human Methyltransferases

Synthesis of 2-aryl-2H-tetrazoles via a regioselective [3+2] cycloaddition reaction

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