Studies on Peptides. XXVIII. Synthesis of the Docosapeptide which Embodies the Entire Amino Acid Sequence of β-Melanocyte-stimulating Hormone from Human Pituitary Gland

Human β-melanocyte-stimulating hormone (MSH), H-Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp-OH (I), was synthesized by deformylation of [21-Ne-formyllysine]-human-β-MSH (IX) by hydrazine acetate. This formyl derivative (IX) was prepared by coupling reaction of Boc-Ala-Glu (OBut)-Lys (Boc)-Lys (Boc)-Asp (OBut)-Glu (OBut)-Gly-pentachlorophenyl ester and H-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys (For)-Asp-OH (II) followed by treatment with trifluoroacetic acid. The latter partially protected pentadecapeptide (II) is the synthetic intermediate of monkey β-MSH (J. Am. Chem. Soc., 90, 527 (1968) ; Chem. Pharm. Bull. (Tokyo), 17, 1229 (1969)) structurally related to human β-MSH. By column chromatography on silica, the former protected heptapeptide active ester was isolated in pure form from the reaction mixture of dicyclohexylcarbodiimide-pentachlorophenol complex and Boc-Ala-Glu (OBut)-Lys (Boc)-Lys (Boc)-Asp (OBut)-Glu (OBut)-Gly-OH, which was prepared by the coupling reaction of Boc-Ala-Glu (OBut)-Lys (Boc)-Lys (Boc)-NHNH2 and H-Asp (OBut)-Glu (OBut)-Gly-OH by the azide procedure. The synthetic human β-MSH and the formyl derivative (IX) exhibited the in vitro MSH activity of 6.2×109 and 3.4×109 units/g respectively.