title: Prometabolites of 5-Diphospho-myo-inositol Pentakisphosphate.
abstract: Diphospho-myo-inositol phosphates (PP-InsP(y)) are an important class of cellular messengers. Thus far, no method for the transport of PP-InsP(y) into living cells is available. Owing to their high negative charge density, PP-InsP(y) will not cross the cell membrane. A strategy to circumvent this issue involves the generation of precursors in which the negative charges are masked with biolabile groups. A PP-InsP(y) prometabolite would require twelve to thirteen biolabile groups, which need to be cleaved by cellular enzymes to release the parent molecules. Such densely modified prometabolites of phosphate esters and anhydrides have never been reported to date. This study discloses the synthesis of such agents and an analysis of their metabolism in tissue homogenates by gel electrophoresis. The acetoxybenzyl-protected system is capable of releasing 5-PP-InsP5 in mammalian cell/tissue homogenates within a few minutes and can be used to release 5-PP-InsP5 inside cells. These molecules will serve as a platform for the development of fundamental tools required to study PP-InsP(y) physiology.
authors.affiliation: Department of Chemistry, University of Zürich (UZH), Winterthurerstrasse 190, 8057 Zürich (Switzerland).
authors.forename: Igor
authors.initials: I
authors.lastname: Pavlovic
authors.affiliation: Department of Chemistry, University of Zürich (UZH), Winterthurerstrasse 190, 8057 Zürich (Switzerland).
authors.forename: Divyeshsinh T
authors.initials: DT
authors.lastname: Thakor
authors.affiliation: Department of Chemistry, University of Zürich (UZH), Winterthurerstrasse 190, 8057 Zürich (Switzerland).
authors.forename: Laurent
authors.initials: L
authors.lastname: Bigler
authors.affiliation: LMCB, University College London (UK).
authors.forename: Miranda S C
authors.initials: MS
authors.lastname: Wilson
authors.affiliation: Center for Plant Molecular Biology, University of Tübingen (Germany).
authors.forename: Debabrata
authors.initials: D
authors.lastname: Laha
authors.affiliation: Center for Plant Molecular Biology, University of Tübingen (Germany).
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schaaf
authors.affiliation: LMCB, University College London (UK).
authors.forename: Adolfo
authors.initials: A
authors.lastname: Saiardi
authors.affiliation: Department of Chemistry, University of Zürich (UZH), Winterthurerstrasse 190, 8057 Zürich (Switzerland). Henningjacob.jessen@chem.uzh.ch.
authors.forename: Henning J
authors.initials: HJ
authors.lastname: Jessen
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002463:Cell Membrane Permeability; D004023:Dictyostelium / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D007295:Inositol Phosphates; C013571:inositol pentaphosphate
keywords: Inositol pyrophosphates; metabolism; protecting groups; second messengers