title: Synthesis of the rosette-inducing factor RIF-1 and analogs.
abstract: Studies on the origin of animal multicellularity have increasingly focused on one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Single cells of S. rosetta can develop into multicellular rosette-shaped colonies through a process of incomplete cytokinesis. Unexpectedly, the initiation of rosette development requires bacterially produced small molecules. Previously, our laboratories reported the planar structure and femtomolar rosette-inducing activity of one rosette-inducing small molecule, dubbed rosette-inducing factor 1 (RIF-1), produced by the Gram-negative Bacteroidetes bacterium Algoriphagus machipongonensis. RIF-1 belongs to the small and poorly explored class of sulfonolipids. Here, we report a modular total synthesis of RIF-1 stereoisomers and structural analogs. Rosette-induction assays using synthetic RIF-1 stereoisomers and naturally occurring analogs defined the absolute stereochemistry of RIF-1 and revealed a remarkably restrictive set of structural requirements for inducing rosette development.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School , 240 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Beemelmanns
authors.forename: Arielle
authors.initials: A
authors.lastname: Woznica
authors.forename: Rosanna A
authors.initials: RA
authors.lastname: Alegado
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Cantley
authors.forename: Nicole
authors.initials: N
authors.lastname: King
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
mesh_terms: D017738:Alkanesulfonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D041963:Bacteroidetes / Q000378:metabolism*; D056897:Choanoflagellata / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009024:Morphogenesis; D013237:Stereoisomerism
chemical_list: D017738:Alkanesulfonic Acids; D008055:Lipids; C015518:sulfolipids