In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt¹-DALDA Analogues.

ABSTRACT: In this study the μ opioid receptor (MOR) ligands DALDA (Tyr-d-Arg-Phe-Lys-NH₂) and Dmt¹-DALDA (Dmt-d-Arg-Phe-Lys-NH₂, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified peptide (3), all peptide analogues derivatized at the C-terminus (4-7) proved to possess high affinity and agonist potency at both MOR and DOR (δ opioid receptor). Results of the Caco-2 monolayer permeation, as well as in vitro blood-brain barrier model experiments, showed that, in the case of compound 4, the glycosylation only slightly diminished the lumen-to-blood and blood-to-lumen transport. Altogether, these ex

SUBMITTER: Ballet S 

PROVIDER: S-EPMC4023695 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature