Synthesis and assay of structural intermediates of crustacean pigment-dispersing hormones (α and β-PDH)

Summary The two characterized crustacean pigment-dispersing hormones (α-PDH; β-PDH) are octadecapeptides which differ in primary structure at six positions. Assays for melanophore pigment-dispersing activity showed β-PDH to be 21-fold more potent than α-PDH. In an effort to explain the difference in potencies between the two PDHs, we synthesized and purified six analogs of α-PDH (Leu4−, Leu11−, Lys13−, Asn16−, Asp17−, and Glu3, Leu4− α-PDH) in which the amino acid residues of α-PDH were substituted with those of β-PDH. Four analogs (Leu11−, Lys13−, Asn16−, and Asp17− α-PDH) possessed melanophore-dispersing activity equivalent to α-PDH. Leu4− α-PDH and Glu3, Leu4− α-PDH were 2.4− and 4-fold more potent than α-PDH, respectively. Glu3-α-PDH was 3.3-fold more potent than α-PDH (Jorenby et al., 1987). These results suggest that the 21-fold increase in activity of β-PDH over α-PDH is due to an interactive effect of two or more substitutions rather than from the product of the effects brought about by individual...