title: Total synthesis of (-)-doliculide, structure-activity relationship studies and its binding to F-actin.
abstract: Actin, an abundant protein in most eukaryotic cells, is one of the targets in cancer research. Recently, a great deal of attention has been paid to the synthesis and function of actin-targeting compounds and their use as effective molecular probes in chemical biology. In this study, we have developed an efficient synthesis of (-)-doliculide, a very potent actin binder with a higher cell-membrane permeability than phalloidin. Actin polymerization assays with (-)-doliculide and two analogues on HeLa and BSC-1 cells, together with a prediction of their binding mode to F-actin by unbiased computational docking, show that doliculide stabilizes F-actin in a similar way to jasplakinolide and chondramide C.
authors.affiliation: Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
authors.forename: Kiran
authors.initials: K
authors.lastname: Matcha
authors.forename: Ashoka V R
authors.initials: AV
authors.lastname: Madduri
authors.forename: Sayantani
authors.initials: S
authors.lastname: Roy
authors.forename: Slava
authors.initials: S
authors.lastname: Ziegler
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: Anna K H
authors.initials: AK
authors.lastname: Hirsch
authors.forename: Adriaan J
authors.initials: AJ
authors.lastname: Minnaard
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D060326:Chemistry Techniques, Synthetic; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000199:Actins; D047630:Depsipeptides; C424144:doliculide