Novel peptides derived from αs1-casein with opioid activity and mucin stimulatory effect on HT29-MTX cells

Abstract

The opioid effect of αs1-casein fragments related to 143AYFYPEL149 and 144YFYPEL149, which had previously shown mucin-stimulatory activity in human goblet cells, was investigated. Peptides 144YFYPEL149 and 144YFYPE148 showed opioid agonistic activity in guinea pig ileum, and in mouse vas deferens but to a lower extent. Peptides were partly hydrolysed during the assay and several of the resulting fragments lost the N-terminal Tyr residue. Docking of peptides 144YFYPEL149 (active) and 144YFYP147 (inactive) into the active site of the opioid receptor model showed remarkable differences regarding the flexibility at the third intracellular loop of the receptor and the interaction with Pro at the peptide C-terminus that forced residues Arg148 and Glu166 from the receptor to move towards the interior of the binding pocket. The study on human cells HT29-MTX has shown that 144YFYPEL149 is the minimum fragment able to stimulate MUC5AC expression.

Keywords

• Opioid peptide
• µ-Opioid receptor
• Molecular dynamics
• Mucin
• Goblet cells