Activity Profiles of Linear, Cyclic Monomer and Cyclic Dimer of Enkephalin

Abstract

The cyclic dimers of enkephalin were isolated as minor components during the solution synthesis of the corresponding cyclic monomers. The ratio of cyclic dimer to monomer was approximately 1:4 from the percent of yields. In the receptor binding assay of two cyclic dimmers, (Tyr2-C[D-Glu-Phe-gPhe]2 6, Tyr2-C[D-AspPhe-gPhe-rLeu]2 8), both analogs exhibited the high preference for δ receptor compared to monocyclic counterparts. In the nociceptive activity, both showed about 5 times less potent than the cyclic monomers. The repeated synthesis of 14-membered cyclic analog, Tyr-C[D-Glu-Phe-gPhe-D-rLeu] 14, which was known as having three distinct cis-trans isomers, gave rise to apparently different conformational analog arousing only trans isomer. In the receptor binding assay, it showed tremendously high selectivity toward μ receptor (δ/μ = 160).

Development of a Highly Active Fluorescence-Based Detector for Yeast G Protein-Coupled Receptor Ste2p

“…All α-factor analogs were prepared using a solid-phase strategy. The procedure followed the synthetic protocol previously described by Hong [17,18]. Target peptides were analyzed by reversed-phase, high-performance liquid chromatography (Shimazdu Prominence HPLC) on an analytical Vydac Everest C18 reversedphase polymer column with detection at 220 nm.…”