181637-41-2Relevant academic research and scientific papers
Synthesis of orthogonally protected lanthionines
Mohd Mustapa, M. Firouz,Harris, Richard,Bulic-Subanovic, Nives,Elliott, Susan L.,Bregant, Sarah,Groussier, Marianne F. A.,Mould, Jessica,Schultz, Darren,Chubb, Nathan A. L.,Gaffney, Piers R. J.,Driscoll, Paul C.,Tabor, Alethea B.
, p. 8185 - 8192 (2007/10/03)
Synthetic approaches to the lantibiotics, a family of thioether-bridged antimicrobial peptides, require flexible synthetic routes to a variety of orthogonally protected derivatives of lanthionine 1. The most direct approaches to lanthionine involve the re
Synthesis and biological activities of cyclic lanthionine enkephalin analogues: δ-opioid receptor selective ligands
Rew, Yosup,Malkmus, Shelle,Svensson, Camilla,Yaksh, Tony L.,Chung, Nga N.,Schiller, Peter W.,Cassel, Joel A.,DeHaven, Robert N.,Goodman, Murray
, p. 3746 - 3754 (2007/10/03)
The synthesis and biological test results of a series of enkephalin analogues incorporating the lanthionine modification are presented. The syntheses of four monosulfide-bridged analogues of enkephalins, Tyr-c[D-AlaL-Gly-Phe-D-AlaL]-OH (1a), Tyr-c[D-ValL-Gly-Phe-D-AlaL]-OH (1b), Tyr-c[D-AlaL-Gly-Phe-AlaL]-OH (1c), and Tyr-c[D-ValL-Gly-Phe-AlaL]-OH (1d), where AlaL and ValL denote the lanthionine amino acid ends linked by a monosulfide bridge to form the lanthionine structure, were successfully carried out via preparation of the linear peptide on solid support and cyclization in solution. In vitro binding assays against μ, δ-, and κ-opioid receptors and in vitro tests using GPI and MVD assays revealed that the dimethyl lanthionine analogues 1b and 1d, denoted as D-ValL in position 2, show substantial selectivity toward the δ-opioid receptor, while the unsubstituted analogues 1a and 1c, denoted as D-AlaL in position 2, bind to both μ- and δ-opioid receptors. The in vivo thermal escape assay by intrathecal administration showed that the analogues 1b and 1d are among the most potent ligands at producing antinociception through the δ-opioid receptor. The picomolar potencies of analogues 1a and 1c in the intrathecal (it.) assay strongly indicate that μ- and δ-opioid receptors interact synergistically to modulate the antinociceptive responses.
