Synthesis and biological activity of beta-melanotropins and analogues

Synthetic [Arg8]-, [Gly10]-, and [Phe12]-beta cl-MSH and beta p-MSH have been prepared by the solid-phase method. Their lipolytic and melanotropic activities have been compared to each other and with those of previously synthesized beta cl-MSH, [formyl-Trp12]-beta cl-MSH, and beta b-MSH. Replacement of Bln8 of beta cl-MSH by Arg causes a greater decrease in melanotropic activity than lipolytic activity. However, when Phe10 of beta cl-MSH is replaced by Gly, both activities are destroyed. Alteration or replacement of Trp12 of beta cl-MSH by formyl-Trp or Phe has little effect on the melanotropic activity while the lipolytic activity is greatly decreased. Replacement of Ser2 of beta b-MSH by Glu induces a three fold increase in melantropic activity but it does not affect the lipolytic activity.