Design and synthesis of a potential SH2 domain inhibitor bearing a stereodiversified 1,4-cis-enediol scaffold

Marian, Christine; Huang, Rong; Borch, Richard F.

doi:10.1016/j.tet.2011.10.014

Cited by 6 publications

(1 citation statement)

References 22 publications

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“…21 Subsequent reductive amination with Boc-protected aspartic aldehyde provided 3 and treatment with propargyl bromide produced 4 . 16,22,23 The N-terminal free amino group of SPKRIA peptide was converted to the azide group on resin by treated with a mixture of triflyl azide, potassium carbonate and copper( II ) sulfate pentahydrate. 24 The azide was then reacted with 4 to form the NAM-peptide conjugate through a triazole linker via click chemistry on resin, followed by a standard peptide cleavage condition to provide the bisubstrate analogue NAM-TZ-SPKRIA.…”

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Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors

et al. 2015

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The protein N-terminal methyltransferase 1 (NTMT1) methylates the α-N-terminal amines of proteins. NTMT1 is upregulated in a variety of cancers and knockdown of NTMT1 results in cell mitotic defects. Therefore, NTMT1 inhibitors could be potential anticancer therapeutics. This study describes the design and synthesis of the first inhibitor targeting NTMT1. A novel bisubstrate analogue (NAM-TZ-SPKRIA) was shown to be a potent inhibitor (Ki = 0.20 μM) for NTMT1 and was selective versus protein lysine methyltransferase G9a and arginine methyltransferase 1. NAM-TZ-SPKRIA was found to exhibit a competitive inhibition pattern for both substrates, and mass spectrometry experiments revealed that the inhibitor substantially suppressed the methylation progression. Our results demonstrate the feasibility of using a triazole group to link an S-adenosyl-L-methionine analog with a peptide substrate to construct bisubstrate analogues as NTMT1 potent and selective inhibitors. This study lays a foundation to further discover small molecule NTMT1 inhibitors to interrogate its biological functions, and suggests a general strategy for the development of selective protein methyltransferase inhibitors.

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Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors

et al. 2015

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Ruthenium, [N-[(1R,2R)/(1S,2S)-2-(Amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]

Ferrié

Fenneteau

Evanno

2014

Encyclopedia of Reagents for Organic Synthesis

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Stereodivergent Synthesis of α‐Aminomethyl Cinnamyl Ethers via Photoredox‐Catalyzed Radical Relay Reaction

Zhang

et al. 2018

Chin. J. Chem.

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A photocatalytic multi‐component radical relay reaction has been developed for the stereodivergent synthesis of both stereoisomers of α‐aminomethyl cinnamyl ethers. The radical relay reaction of hydroxylamine derivatives, enol ethers and alkenyl boronic acids in DMSO under white LEDs could lead to E‐isomers of α‐aminomethyl cinnamyl ethers. The E‐isomers could subsequently isomerize to less thermodynamically stable Z‐isomers under blue LEDs using toluene as the co‐solvent in a one‐pot manner.

show abstract

Design and synthesis of a potential SH2 domain inhibitor bearing a stereodiversified 1,4-cis-enediol scaffold

Cited by 6 publications

References 22 publications

Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors

Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors

Ruthenium, [N-[(1R,2R)/(1S,2S)-2-(Amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]

Stereodivergent Synthesis of α‐Aminomethyl Cinnamyl Ethers via Photoredox‐Catalyzed Radical Relay Reaction

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