title: Lynamicin D an antimicrobial natural product affects splicing by inducing the expression of SR protein kinase 1.
abstract: The first total synthesis of the antimicrobial natural product lynamicin D has been developed using a Suzuki coupling to construct the bisindole pyrrole skeleton. An evaluation of the biological activity of lynamicin D reveals that it has a minor effect on cell viability but it can modulate splicing of pre-mRNAs. We provide evidence that this effect is mainly due to the ability of lynamicin D to alter the levels of SRPK1, the key kinase involved in both constitutive and alternative splicing.
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sigala
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Ganidis
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Savvas
authors.initials: S
authors.lastname: Thysiadis
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Alexandros L
authors.initials: AL
authors.lastname: Zografos
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Giannakouros
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece. Electronic address: sarli@chem.auth.gr.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Sarli
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Nikolakaki
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D007211:Indoles; D011758:Pyrroles; C000621707:lynamicin D; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Bisindole pyrroles; Bisindolyl alkaloids; Lynamicin D; SRPK1; mRNA splicing