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

The solid‐phase syntheses of [Sar²]‐, [Ala²]‐, [D‐Leu²]‐, [D‐Lys²]‐β‐ endorphins and [Pro⁵]‐, [Leu⁵]‐, [D‐Leu⁵]‐, [D‐Ala², D‐Leu⁵]‐β‐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, thin‐layer chromatography, paper electrophoresis, and amino acid analyses of acid and enzymic hydrolysates. Bioassay of the synthetic analogs for analgesic activity by the tail‐flick method showed the D‐Leu² analog to be 48% as potent as β_h‐endorphin while the Ala², D‐Lys², Leu⁵, and [D‐Ala², D‐Leu⁵] analogs were 8 to 17% as active. The Sar², D‐Leu⁵, and Pro⁵ analogs were less than 1% as potent.