title: Functional non-nucleoside adenylyl cyclase inhibitors.
abstract: In this study, we describe the synthesis of novel functional non-nucleoside adenylyl cyclase inhibitors, which can be easily modified with thiol containing biomolecules such as tumour targeting structures. The linkage between inhibitor and biomolecule contains cleavable bonds to enable efficient intracellular delivery in the reductive milieu of the cytosol as well as in the acidic environment within endosomes and lysosomes. The suitability of this synthetic approach was shown by the successful bioconjugation of a poor cell-permeable inhibitor with a cell-penetrating peptide. Additionally, we have demonstrated the excellent inhibitory effect of the compounds presented here in a live-cell Förster resonance energy transfer-based assay in human embryonic kidney cells.
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Lelle
authors.forename: Abdul
authors.initials: A
authors.lastname: Hameed
authors.forename: Lisa-Maria
authors.initials: LM
authors.lastname: Ackermann
authors.forename: Stefka
authors.initials: S
authors.lastname: Kaloyanova
authors.forename: Manfred
authors.initials: M
authors.lastname: Wagner
authors.forename: Filip
authors.initials: F
authors.lastname: Berisha
authors.forename: Viacheslav O
authors.initials: VO
authors.lastname: Nikolaev
authors.forename: Kalina
authors.initials: K
authors.lastname: Peneva
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000378:metabolism; D015374:Biosensing Techniques; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006801:Humans; D007545:Isoproterenol / Q000737:chemistry
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D057846:Cell-Penetrating Peptides; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol
keywords: adenylyl cyclase inhibitor; cancer treatment; pyridyl disulphide; tumour targeting