Cryptides are bioactive peptides hidden in various functional protein structures and thought to be produced by proteolysis during protein maturation and degradation processes [1]. Recently, many evidences that indicate their biological roles are accumulated. Their cellular signaling mechanisms have been also investigated and it was demonstrated the presence of their own receptor molecules. Therefore, it has been paid attention to the physiological significance of cryptides as non-classical bioactive peptides.

Previously, we purified and identified three neutrophil-activating cryptides, mitocryptide-1, mitocryptide-2, and mitocryptide-CYC from healthy porcine hearts [2-4], and also suggested the presence of many mitochondrial protein-derived neutrophil-activating cryptides. In the study, mitochondrial protein-derived fragmented peptides having common features in the distributions of positively-charged and hydrophobic amino acid residues nevertheless their primary sequences were suggested to exhibit the abilities to activate neutrophils. In the present study, we attempted to identify novel neutrophil-activating cryptides systematically utilizing multiple solid phase peptide synthesis, protein data base, and MS/MS analysis.

[1] Ueki, N., Someya, K., Matsuo, Y., Wakamatsu, K., Mukai, H. (2007)Biopolymers (Pep. Sci.), 88, 190–198. [2] Mukai, H., Hokari, Y., Seki, T., Takao, T., Kubota, M., Matsuo, Y., Tsukagoshi, H., Kato, M., Kimura, H., Shimonishi, Y., Kiso, Y., Nishi, Y., Wakamatsu, K., Munekata, E. (2008) J. Biol. Chem., 283, 30596–30605. [3] Mukai, H., Seki, T., Nakano, H., Hokari, Y., Takao, T., Kawanami, M., Tsukagoshi, H., Kimura, H., Kiso, Y., Shimonishi, Y., Nishi, Y., Munekata, E. (2009) J. Immunol., 182, 5072–5080. [4] Hokari, Y., Seki, T., Nakano, H., Matsuo, Y., Fukamizu, A., Munekata, E., Kiso, Y., Mukai, H. (2012) Prot. Pept. Lett., 19, 680–687.