Structure-Activity Relationship Studies of N- and C-Terminally Modified Secretin Analogs for the Human Secretin Receptor
| Autor: | Billy K. C. Chow, Jérôme Leprince, Kailash Singh, Ahmed Aa Allam, Jamaan S. Ajarem, Aloysius Wilfred Raj Arokiaraj, Vijayalakshmi Senthil, David Vaudry, Benjamin Lefranc |
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| Přispěvatelé: | Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of Hong Kong (HKU), King Saud University [Riyadh] (KSU), Beni-Suef University |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Peptide Hormones [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology lcsh:Medicine Plasma protein binding MESH: Amino Acid Sequence MESH: Receptors G-Protein-Coupled [CHIM.THER]Chemical Sciences/Medicinal Chemistry [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Biochemistry Fluorophotometry Receptors G-Protein-Coupled Secretin Binding Analysis Spectrum Analysis Techniques 0302 clinical medicine MESH: Structure-Activity Relationship Drug Discovery [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] Cyclic AMP Fluorescence Resonance Energy Transfer Post-Translational Modification lcsh:Science Peptide sequence MESH: Cyclic AMP ComputingMilieux_MISCELLANEOUS MESH: Secretin 0303 health sciences Crystallography Multidisciplinary MESH: Peptides Physics Condensed Matter Physics 3. Good health Molecular Docking Simulation Spectrophotometry 030220 oncology & carcinogenesis Physical Sciences Crystal Structure Sequence Analysis Signal Peptides Protein Binding Research Article Signal Transduction Agonist Transmembrane Receptors medicine.drug_class Molecular Sequence Data Allosteric regulation Secretin receptor family Biology Research and Analysis Methods Receptors Gastrointestinal Hormone Structure-Activity Relationship 03 medical and health sciences MESH: Drug Discovery medicine MESH: Molecular Docking Simulation Humans Solid State Physics MESH: Protein Binding Amino Acid Sequence Molecular Biology Techniques Sequencing Techniques Molecular Biology Chemical Characterization 030304 developmental biology G protein-coupled receptor MESH: Humans MESH: Molecular Sequence Data 030102 biochemistry & molecular biology MESH: Receptors Gastrointestinal Hormone lcsh:R Correction Biology and Life Sciences Proteins Cell Biology Hormones 030104 developmental biology Docking (molecular) [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology lcsh:Q G Protein Coupled Receptors Peptides Sequence Alignment |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2016, 11 (3), ⟨10.1371/journal.pone.0149359⟩ PLoS ONE, Public Library of Science, 2016, 11 (3), pp.e0149359. ⟨10.1371/journal.pone.0149359⟩ PLoS ONE, Public Library of Science, 2016, 11 (10), ⟨10.1371/journal.pone.0165770⟩ PLoS ONE, Vol 11, Iss 10, p e0165770 (2016) PLoS ONE, Vol 11, Iss 3, p e0149359 (2016) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0149359⟩ |
| Popis: | The pleiotropic role of human secretin (hSCT) validates its potential use as a therapeutic agent. Nevertheless, the structure of secretin in complex with its receptor is necessary to develop a suitable therapeutic agent. Therefore, in an effort to design a three-dimensional virtual homology model and identify a peptide agonist and/or antagonist for the human secretin receptor (hSR), the significance of the primary sequence of secretin peptides in allosteric binding and activation was elucidated using virtual docking, FRET competitive binding and assessment of the cAMP response. Secretin analogs containing various N- or C-terminal modifications were prepared based on previous findings of the role of these domains in receptor binding and activation. These analogs exhibited very low or no binding affinity in a virtual model, and were found to neither exhibit in vitro binding nor agonistic or antagonistic properties. A parallel analysis of the analogs in the virtual model and in vitro studies revealed instability of these peptide analogs to bind and activate the receptor. published_or_final_version |
| Databáze: | OpenAIRE |
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