β-Endorphin: synthesis and properties of analogs modified in positions 8 and 31

Four analogs of human β-endorphin (β_h-EP) were synthesized by the solid-phase method: [Gln^8.31]-β_h-EP(I), [Arg⁸, Gln³¹] -β_h-EP(II), [Ala⁸, Gln³¹] -β_h-EP (III), and [Val⁸, Gln³¹]-β_h-EP(IV). Radioreceptor binding assay with use of tritiated β_h-EP as primary ligand gave relative potencies as follows: β_h-EP, 100; I, 200; II, 150; III, 150; IV, 120. Relative potencies in an analgesic assay were: β_h-EP, 100; 1,236; II, 254;III, 116; IV, 121. The side-chain of Glu-8 in β_h-EP can be replaced by a variety of structures without diminishing biological activity.