Peptides containing a D-amino acid isolated from molluscs

We have been screening biologically active peptides from the ganglia and heart tissues of the African giant snail, Achatina fulica. Two novel peptides were isolated and named achatin-I and fulicin. Each peptide contained a D-amino acid residue at the second position. Achatin-I enhanced the cardiac activity by exciting the heart excitatory neuron in the central nervous system and peripherally by increasing the frequency and the amplitude of the ventricular beat. Fulicin potentiated the contraction of the penis retractor muscle. Fulicin-like immunoreactivities were found in the nerve fibers innervating the muscle, and fulicin-like substances were scattered in the muscle. Fulicin was suggested to be involved in the regulation of the muscle contraction. The cDNA encoding the precursor protein of fulicin revealed that the D-Asn residue of fulicin was encoded by the normal codon. It was suggested that novel post-translational L-/D-isomerization process was involved in the biosynthesis of fulicin. Three possible roles of D-amino acids have been discussed as follows: 1) Specific stereostructures which may be suitable for binding to receptor molecules can be stabilized by the presence of D-amino acid residue. 2) The D-amino acid residue may modulate the biological activity of the peptide, thereby generating biological diversity. 3) The presence of D-amino acids may increase the resistance to enzymatic degradation and prolong biological life of peptides. Since we have found the peptide which may not be involved to three categories mentioned above, more discussion will be necessary to clarify the physiological roles of D-amino acids.