Design of a disulfide-less, pharmacologically inert, and chemically competent analog of maurocalcine for the efficient transport of impermeant compounds into cells
| العنوان: | Design of a disulfide-less, pharmacologically inert, and chemically competent analog of maurocalcine for the efficient transport of impermeant compounds into cells |
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| المؤلفون: | Michel De Waard, Narendra Ram, Norbert Weiss, Sonia Aroui, Fabienne Pirollet, Vincent Jacquemond, Nicolas Andreotti, Hervé Darbon, Isabelle Texier-Nogues, Jean-Marc Sabatier, Michel Ronjat |
| المساهمون: | Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie intégrative, cellulaire et moléculaire (PICM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ERT 62 Ambrilia Biopharma S.A., Université de la Méditerranée - Aix-Marseille 2, Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Inserm, Fonds de valorisation du Commissariat à l'Energie Atomique, Région Rhône-Alpes bourse Emergence pour doctorant, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Canepari, Marco |
| المصدر: | Journal of Biological Chemistry Journal of Biological Chemistry, 2008, 283 (40), pp.27048-56. ⟨10.1074/jbc.M804727200⟩ Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (40), pp.27048-56. ⟨10.1074/jbc.M804727200⟩ |
| بيانات النشر: | HAL CCSD, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Stereochemistry, Lysine, Scorpion Venoms, MESH: Cricetinae, Peptide, CHO Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biochemistry, Article, Scorpions, Mice, 03 medical and health sciences, Residue (chemistry), Cricetulus, MESH: Scorpion Venoms, MESH: Cricetulus, MESH: CHO Cells, Cricetinae, Animals, Humans, MESH: Animals, MESH: Disulfides, Disulfides, Muscle, Skeletal, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, chemistry.chemical_classification, Drug Carriers, 0303 health sciences, MESH: Muscle, Skeletal, MESH: Humans, Chemistry, Ryanodine receptor, 030302 biochemistry & molecular biology, Biological activity, Cell Biology, MESH: Scorpions, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, MESH: Drug Carriers, Biotinylation, Maurocalcine, Cysteine |
| الوصف: | International audience; Maurocalcine is a 33-mer peptide initially isolated from the venom of a Tunisian scorpion. It has proved itself valuable as a pharmacological activator of the ryanodine receptor and has helped the understanding of the molecular basis underlying excitation-contraction coupling in skeletal muscles. Because of its positively charged nature, it is also an innovative vector for the cell penetration of various compounds. We report a novel maurocalcine analog with improved properties: (i) the complete loss of pharmacological activity, (ii) preservation of the potent ability to carry cargo molecules into cells, and (iii) coupling chemistries not affected by the presence of internal cysteine residues of maurocalcine. We did this by replacing the six internal cysteine residues of maurocalcine by isosteric 2-aminobutyric acid residues and by adding an additional N-terminal biotinylated lysine (for a proof of concept analog) or an N-terminal cysteine residue (for a chemically competent coupling analogue). Additional replacement of a glutamate residue by alanyl at position 12 further improves the potency of these analogues. Coupling to several cargo molecules or nanoparticles are presented to illustrate the cell penetration potency and usefulness of these pharmacologically inactive analogs. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0021-9258 1083-351X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e67c1748f4914ce57f5ca6a6a67669d https://www.hal.inserm.fr/inserm-00355685/file/MM-Abu-revised-ver2-fig.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2e67c1748f4914ce57f5ca6a6a67669d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219258 1083351X |
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