Susanna Borg, Roeland C. Vollinga, Maryse Labarre
1999
Citations
0
Influential Citations
114
Citations
Quality indicators
Journal
Journal of Medicinal Chemistry
Abstract
Enantiopure heterocyclic Boc-protected Phe-Gly dipeptidomimetics containing 1,3,4-oxadiazole, 1,2,4-oxadiazole, and 1,2,4-triazole ring systems have been synthesized as building blocks in the synthesis of pseudopeptides. Three derivatives (1−3) have the carboxylic acid function directly bound to the heterocyclic ring, and three derivatives (4−6) have an extra methylene group between the heterocyclic ring and the acid function to allow for an increased conformational flexibility. The mimetics were used as Phe-Gly replacements in the biologically active peptides dermorphin (Tyr-d-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2, SP). The pseudopeptide synthesis was performed using solid-phase methodology on a MBHA-resin using Boc-chemistry. The biological evaluation was performed by testing the μ- and δ-opioid receptor affinities of the dermorphin pseudopeptides and the NK1 receptor affinities of the SP pseudopeptides. The results showed that all mimetics except 3...