CAP-1 is a cuticle peptide isolated from the acid-insoluble fraction of the exoskeleton of the crayfish Procambarus clarkii. CAP-1 is an acidic peptide and comprises 78 amino acid residues. The C-terminal part is especially highly acidic by a phosphoserine and an Asp-repeat, which is thought to be responsible for the calcification inhibitory activity in vitro. To examine the significance of the Asp-repeat and to get information on structure-activity relationship, various small related peptides with different sequences were synthesized and tested for the inhibitory activity. The results showed that 1) the activity depends not on the Asp-containing sequence but on the total number of Asp residues, 2) peptide conformation does not affect the activity, and 3) Asp is more effective in inhibitory activity than Glu. These characteristics seem to be consistent with the fact that acidic matrix proteins identified so far from various biominerals have almost no sequence similarity, leading to the idea that the molecular evolution of matrix proteins and peptides in biominerals might be intrinsically different from that of enzymes, hormones and other important functional proteins possibly due to the difference in the mode of interaction between proteins and inorganic compounds, or between proteins and organic compounds.