Fusicoccins (FCs) exhibit variousc ellular activities in mammalian cells, but detailso ft he mechanism of action are not fully understood. In this study,w esynthesized two pairs of model derivatives of FCs differing only in the presence and absence of a1 2-hydroxyl group and evaluated their binding to a1 4-3-3 protein together with various mode 1a nd mode 3p hosphopeptide ligands. Our results demonstrate that the 12-hydroxyl group hampersb inding to 14-3-3 with mode 1p hospholigands,p resumably due to steric repulsion with the i+ +2r esidue. Furthermore, cellbased evaluations showedt hat only non-substituted FCs exhibit significant cytotoxicity and all 12-hydroxyl derivatives were inactive, demonstrating ac lear correlation with their ability to form ternary complexes with 14-3-3 and am ode 1 ligand.T hese results suggest that binding to 14-3-3 and a partner protein(s) possessing am ode 1s equence plays a role in the mechanism of action of 12-non-substituted FCs.[a] Prof.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/chem.201804428:Experimental details for synthesis, in vitro evaluation,and cell-based experiments.
Fusicoccin, a phytotoxic diterpene glucoside, was converted to a series of antiproliferative agents for tumor cells by removing 12‐hydroxyl group semi‐synthetically. These compounds were shown to upregulate interaction of 14‐3‐3 and a phospholigand in a sequence‐specific manner. More information can be found in the Full Paper by J. Ohkanda et al. on page 16066.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.