title: Synthesis of a simplified bryostatin C-ring analogue that binds to the CRD2 of human PKC-alpha and construction of a novel BC-analogue by an unusual Julia olefination process.
abstract: [structure: see text] The synthesis of two truncated bryostatin analogues 2 and 3 is described. High-field NMR measurements on the C-ring analogue 3 in C(2)H(3)CN containing 25% (2)H(2)O have shown that it binds to the CRD2 of human PKC-alpha at virtually the same position as phorbol-13-acetate (PA) and bryostatin 1 (1). NMR titration studies have also revealed that 3 binds to the CRD2 with a potency similar in magnitude to PA but much less potently than 1.
authors.affiliation: The Christopher Ingold Laboratories, University College London, 20 Gordon Street, London WC1H 0AJ, England. k.j.hale@ucl.ac.uk
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Hale
authors.forename: Mark
authors.initials: M
authors.lastname: Frigerio
authors.forename: Soraya
authors.initials: S
authors.lastname: Manaviazar
authors.forename: Marc G
authors.initials: MG
authors.lastname: Hummersone
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Fillingham
authors.forename: Igor G
authors.initials: IG
authors.lastname: Barsukov
authors.forename: Christian F
authors.initials: CF
authors.lastname: Damblon
authors.forename: Andreas
authors.initials: A
authors.lastname: Gescher
authors.forename: Gordon C K
authors.initials: GC
authors.lastname: Roberts
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D054713:Bryostatins; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism; D018942:Macrolides; D019906:Nuclear Magnetic Resonance, Biomolecular; D010703:Phorbol Esters; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism; D051571:Protein Kinase C-alpha; D013329:Structure-Activity Relationship; D017186:Titrimetry
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; D010703:Phorbol Esters; C050164:phorbol 13-monoacetate; C046785:bryostatin 1; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha