β-ENDORPHIN: SYNTHESIS AND ANALGESIC ACTIVITY OF SEVERAL ANALOGS MODIFIED IN POSITIONS 2 AND 5

Abstract

The solid-phase syntheses of [Sar2]-, [Ala2]-, [D-Leu2]-, [D-Lys2]-.beta.-endorphins and [Pro5]-, [Leu-5]-, [D-Leu5]-, [D-Ala2, D-Leu5]-.beta.-endorphins are described. The synthetic peptides were purified by chromatography on carboxymethylcellulose and partition chromatography on Sephadex G-50. They were characterized by partition chromatography on agarose, TLC, paper electrophoresis and amino acid analyses of acid and enzymic hydrolysates. Bioassay of the synthetic analogs for analgesic activity by the tail-flick method [in mice] showed the D-Leu2 analog to be 48% as potent as .beta.h-endorphin while the Ala2, D-Lys2, Leu5 and [D-Ala2, D-Leu5] analogs were 8-17% as active. The Sar2, D-Leu5 and Pro5 analogs were < 1% as potent.