We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Phosphorylation of enkephalins: NMR and CD studies in aqueous and membrane-mimicking environments.
- Authors
Yeomans, Larisa; Muthu, Dhanasekaran; Lowery, John J; Martinez, Heather N; Abrell, Leif; Lin, Guanxin; Strom, Kyle; Knapp, Brian I; Bidlack, Jean M; Bilsky, Edward J; Polt, Robin
- 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 μ/δ-agonist, and one related to DAMGO, a highly selective μ-agonist. Each unglycosylated peptide was compared to its phosphate, its mono-benzylphosphate ester, and its β-d-glucoside. Binding was characterized in membrane preparations from Chinese hamster ovary cells expressing human μ, δ and κ-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.
- Publication
Chemical biology & drug design, 2011, Vol 78, Issue 5, p749
- ISSN
1747-0285
- Publication type
Journal Article
- DOI
10.1111/j.1747-0285.2011.01203.x