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Synthesis and Evaluation of Ginkgolic Acid Derivatives as SUMOylation Inhibitors.

ABSTRACT: SUMOylation has emerged as an important post-translational modification that has been shown to modulate protein activity associated with various signaling pathways, and consequently, it has emerged as an important therapeutic target. While several natural products have been shown to inhibit enzymes involved in the SUMOylation process, there has been little progress toward the development of more selective and potent SUMOylation inhibitors. Ginkgolic acid was one of the first natural products discovered to inhibit the SUMO E1 enzyme. Despite its use to mechanistically investigate the SUMOylation process, ginkgolic acid also modulates other pathways as well. In this Letter, preliminary structure-activity relationships for ginkgolic acid as a SUMOylation inhibitor are presented.

SUBMITTER: Brackett CM

PROVIDER: S-EPMC7667826 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of Ginkgolic Acid Derivatives as SUMOylation Inhibitors.

Brackett Christopher M CM García-Casas Ana A Castillo-Lluva Sonia S Blagg Brian S J BSJ

ACS medicinal chemistry letters 20200924 11

SUMOylation has emerged as an important post-translational modification that has been shown to modulate protein activity associated with various signaling pathways, and consequently, it has emerged as an important therapeutic target. While several natural products have been shown to inhibit enzymes involved in the SUMOylation process, there has been little progress toward the development of more selective and potent SUMOylation inhibitors. Ginkgolic acid was one of the first natural products dis ...[more]

PMID: 33214832

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