A biotinylated peptide, BP21, as a novel potent anti-anaphylactic agent targeting platelet-activating factor.

Platelet-activating factor (PAF) is an important mediator of anaphylaxis and is therefore an anti-anaphylactic drug target. We recently reported that synthetic N-terminally biotinylated peptides (BP4-BP29) inhibit PAF by directly interacting with PAF and its metabolite/precursor lyso-PAF. In this study, we investigated whether the biotinylated peptides can inhibit anaphylactic reactions in vivo. In mouse models of anaphylaxis, one of the peptides, BP21, markedly and dose-dependently inhibited hypothermia with a maximum dose-response within 30 min after administration, even at doses 20 times lesser than doses of the known PAF antagonist CV-3988. In contrast, the anti-hypothermic effect of BGP21, in which the Tyr-Lys-Asp-Gly sequence in BP21 was modified to a Gly-Gly-Gly-Gly sequence, was less than that of BP21. The alanine scanning and shuffling the amino acid residues of BP4 (Tyr-Lys-Asp-Gly) demonstrated that the Tyr-Lys-Asp-Gly consensus sequence is important for the inhibitory effect of the peptide on hypothermia. BP21 also suppressed vascular permeability during anaphylaxis with a maximum dose-response within 30 min of administration. In a rat model of hind paw oedema, BP21 significantly inhibited the oedema induced by PAF but not that induced by the other pro-inflammatory mediators, such as histamine, serotonin, and bradykinin. Tryptophan fluorescence measurements showed that BP21 interacted with PAF, but not with histamine, serotonin, or bradykinin. In contrast, BGP21 did not interact with PAF. These results suggest that biotinylated peptides, especially BP21, can specifically and markedly inhibit anaphylactic reactions in vivo and that this involves direct interaction of its Tyr-Lys-Asp-Gly region with PAF. Therefore, a biotinylated peptide, BP21, can be used as novel potential anti-anaphylactic drugs targeting PAF. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.