title: Retro-1 Analogues Differentially Affect Oligonucleotide Delivery and Toxin Trafficking.
abstract: Retro-1 is a small molecule that displays two important biological activities: First, it blocks the actions of certain toxins by altering their intracellular trafficking. Second, it enhances the activity of oligonucleotides by releasing them from entrapment in endosomes. This raises the question of whether the two actions involve the same cellular target. Herein we report the effects of several Retro-1 analogues on both toxins and oligonucleotides. We found analogues that affect toxins but not oligonucleotides and vice-versa, while Retro-1 is the only compound that affects both. This indicates that the molecular target(s) involved in the two processes are distinct.
authors: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors: Bing
authors: B
authors: Yang
authors: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors: Xin
authors: X
authors: Ming
authors: Service de Chimie Bio-organique et Marquage (SCBM), IBITECS, CEA, LabEx LERMIT, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
authors: Hajer
authors: H
authors: Abdelkafi
authors: Service de Chimie Bio-organique et Marquage (SCBM), IBITECS, CEA, LabEx LERMIT, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
authors: Valerie
authors: V
authors: Pons
authors: Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, CEA, LabEx LERMIT, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
authors: Aurelien
authors: A
authors: Michau
authors: Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, CEA, LabEx LERMIT, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
authors: Daniel
authors: D
authors: Gillet
authors: Service de Chimie Bio-organique et Marquage (SCBM), IBITECS, CEA, LabEx LERMIT, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
authors: Jean-Christophe
authors: JC
authors: Cintrat
authors: Service de Chimie Bio-organique et Marquage (SCBM), IBITECS, CEA, LabEx LERMIT, Université Paris-Saclay, 91191, Gif-sur-Yvette, France.
authors: Julien
authors: J
authors: Barbier
authors: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors: Rudy
authors: 0000-0002-9107-6603
authors: R
authors: Juliano
mesh_terms: D001570:Benzodiazepinones / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry*; D022621:Shiga Toxin / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C549072:7-bromo-5-phenyl-4-propionyl-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one; D001570:Benzodiazepinones; D004337:Drug Carriers; D009841:Oligonucleotides; D054852:Small Molecule Libraries; D022621:Shiga Toxin
keywords: Retro-1; endocytosis; oligonucleotides; toxins; trafficking