Human beta-endorphin. Synthesis and biological activity of analogs with modifications in residue positions 3, 4 or 5

Three analogs of human beta-endorphin (beta h-EP) have been synthesized by the solid-phase method: [Phe2, Gly4]-beta h-EP(I), [Tyr5]-beta h-EP (II), and [Trp5[-beta h-ET (III). Analogs I and II are related to the highly potent hybrid analog [dermorphin1-7]-beta c-EP (beta c-EP). Radio-receptor-binding and analgesic assays gave relative potencies as follows, respectively: beta h-FP, 100, 100; I, 51, 43; II, 64, 30; III, 15, 4. The high potency of [dermorphin 1-7]-beta c-EP is not due to any one of the following structural elements: D-Ala2, Phe3-Gly4, Tyr5, and Pro6. Increasing hydrophobicity in position 5 (Met in beta-EP) leads to decreasing biological activity.