title: Structure-Activity Relationship Studies of N- and C-Terminally Modified Secretin Analogs for the Human Secretin Receptor.
abstract: 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.
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
authors.forename: Kailash
authors.initials: K
authors.lastname: Singh
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Senthil
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
authors.forename: Aloysius Wilfred Raj
authors.initials: AW
authors.lastname: Arokiaraj
authors.affiliation: Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Neurotrophic Factors and Neuronal Differentiation Team, Inserm U982, Associated International Laboratory Samuel de Champlain, Regional Platform for Cell Imaging of Haute-Normandie (PRIMACEN), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.affiliation: Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Neurotrophic Factors and Neuronal Differentiation Team, Inserm U982, Associated International Laboratory Samuel de Champlain, Regional Platform for Cell Imaging of Haute-Normandie (PRIMACEN), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lefranc
authors.affiliation: Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Neurotrophic Factors and Neuronal Differentiation Team, Inserm U982, Associated International Laboratory Samuel de Champlain, Regional Platform for Cell Imaging of Haute-Normandie (PRIMACEN), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.|Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Allam
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Jamaan
authors.initials: J
authors.lastname: Ajarem
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
authors.forename: Billy K C
authors.initials: BK
authors.lastname: Chow
mesh_terms: D000595:Amino Acid Sequence; D000242:Cyclic AMP / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012633:Secretin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin; D000242:Cyclic AMP