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- W2796352849 abstract "Despite its promising biological profile, the cellular targets of iriomoteolide-3a, a novel 15-membered macrolide isolated from Amphidinium sp., have remained unknown. A small library of non-natural iriomoteolide-3a analogues is presented here as a result of a novel, highly convergent, catalysis-based scaffold-diversification campaign, which revealed the suitable sites for chemical editing in the original core. We provide compelling experimental evidence for actin as one of iriomoteolides' primary cellular targets, establishing the ability of these secondary metabolites to inhibit cell migration, induce severe morphological changes in cells and cause a reversible cytoplasmic retraction and reduction of F-actin fibers in a time and dose dependent manner. These results are interpreted in light of the ability of iriomoteolides to stabilize F-actin filaments. Molecular dynamics simulations provide evidence for iriomoteolide-3a binding to the barbed end of G-actin. These results showcase iriomoteolides as novel and easily tunable chemical probes for the in vitro study of actin dynamics in the context of cell motility processes including cell invasion and division." @default.
- W2796352849 created "2018-04-13" @default.
- W2796352849 creator A5006965455 @default.
- W2796352849 creator A5014753652 @default.
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- W2796352849 creator A5046421499 @default.
- W2796352849 creator A5053085529 @default.
- W2796352849 creator A5062050554 @default.
- W2796352849 date "2018-01-01" @default.
- W2796352849 modified "2023-10-17" @default.
- W2796352849 title "Iriomoteolides: novel chemical tools to study actin dynamics" @default.
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