Synthesis and biological evaluation of leucine enkephalin turn mimetics
2006 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, Vol. 4, no 3, 416-423 p.Article in journal (Refereed) Published
A cyclic Leu-enkephalin mimetic containing a 7-membered ring, and two linear analogues, has been prepared on solid phase. In the cyclic mimetic the intramolecular (1–4) hydrogen bond found in crystalline Leu-enkephalin has been replaced by an ethylene bridge. In addition, the amide bond between Tyr1 and Gly2 has been replaced by a methylene ether isostere and Gly3 has been deleted. The two linear analogues both contain the methylene ether isostere instead of the Tyr1-Gly2 amide bond and the shorter of the two lacks Gly3. The three compounds, and a β-turn mimetic analogous to the 7-membered turn mimetic but with Gly3 included, were evaluated for specific binding to µ- and δ-opioid receptors in rat brain membranes. With the exception of the β-turn mimetic the three other Leu-enkephalin analogues all bound with varying affinity to the µ- and δ-opioid receptors. From the results it could be concluded that Leu-enkephalin binds in a turn conformation to the opiate receptors, but that this conformation is not a (1–4) β-turn.
Place, publisher, year, edition, pages
2006. Vol. 4, no 3, 416-423 p.
Animals, Biomimetic Materials/*chemical synthesis/chemistry/metabolism/*pharmacology, Brain/cytology, Cyclization, Enkephalin; Leucine/*analogs & derivatives/*chemistry, Ligands, Molecular Structure, Rats, Receptors, Opioid, delta/metabolism, Receptors, Opioid, mu/metabolism
IdentifiersURN: urn:nbn:se:umu:diva-2274DOI: 10.1039/b515618aOAI: oai:DiVA.org:umu-2274DiVA: diva2:140203