Structure-Activity Relationship Studies of N- and C-Terminally Modified Secretin Analogs for the Human Secretin Receptor - Normandie Université Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2016

Structure-Activity Relationship Studies of N- and C-Terminally Modified Secretin Analogs for the Human Secretin Receptor

Résumé

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.

Dates et versions

hal-01974202 , version 1 (08-01-2019)

Identifiants

Citer

Kailash Singh, Vijayalakshmi Senthil, Aloysius Wilfred Raj Arokiaraj, Jérôme Leprince, Benjamin Lefranc, et al.. Structure-Activity Relationship Studies of N- and C-Terminally Modified Secretin Analogs for the Human Secretin Receptor. PLoS ONE, 2016, 11 (3), pp.e0149359. ⟨10.1371/journal.pone.0149359⟩. ⟨hal-01974202⟩
34 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More