Phosphorylation of enkephalins: NMR and CD studies in aqueous and membrane-mimicking environments.

ABSTRACT: Phosphorylation of l-serine-containing enkephalin analogs has been explored as an alternative to glycosylation in an effort to increase blood-brain barrier permeability and CNS bioavailability of peptide pharmacophores. Two enkephalin-based peptides were modified for these studies, a set related to DTLES, a mixed ?/?-agonist, and one related to DAMGO, a highly selective ?-agonist. Each unglycosylated peptide was compared to its phosphate, its mono-benzylphosphate ester, and its ?-d-glucoside. Binding was characterized in membrane preparations from Chinese hamster ovary cells expressing human ?, ? and ?-opiate receptors. Antinociception was measured in mice using the 55 °C tail-flick assay. To estimate bioavailability, the antinociceptive effect of each opioid agonist was evaluated after intracerebroventricular (i.c.v.) or intravenous administration (i.v.) of the peptides. Circular dichroism methods and high-field nuclear magnetic resonance were used in the presence and absence of sodium dodecylsulfate to understand how the presence of a membrane might influence the peptide conformations.

SUBMITTER: Yeomans L 

PROVIDER: S-EPMC3193572 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature