Novel biological effects of alloferon and its selected analogues: Structure–activity study

• Alloferon and selected alloferon-derived peptides were evaluated for pro-apoptotic and myotropic activity.
• Alloferon and peptides: Phe(p-NH2)1]-, [Tyr6]- and [1–10]-alloferon strongly induce apoptosis in cells in vivo.
• Alloferon and its selected analogues show a weak cardiostimulatory activity in Z. atratus in vitro.
• The structure–activity relationship of alloferon is discussed.

The subject of this paper is a search for new biological properties of alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) and a series of its analogues. The studies on structure/activity relationship in alloferon, the synthesis of a series of 28 analogues were performed. The analogues were modified at position 1 or 6, and other were oligopeptides with a shortened peptide sequence. Biological effects of the peptides were evaluated by the pro-apoptotic action in vivo on haemocytes of Tenebrio molitor and in the cardiotropic test in vitro on the heart of T. molitor and Zophobas atratus. In the in vivo bioassays, new biological activities of alloferon and its analogues were discovered. In haemocytotoxic bioassay, alloferon strongly induces T. molitor haemocytes to undergo apoptosis at a dose of 10 nM. Moreover, [Phe(p-NH2)1]-, [Tyr6]- and [1-10]-alloferon exhibit a two-fold increase of caspases activation in comparison with the alloferon. However, alloferon and its analogues show a weak cardiostimulatory activity in Z. atratus but the heart of T. molitor is not sensitive to these peptides. The results obtained here suggest that alloferon plays pleiotropic functions in insects.

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