A biotinylated peptide, BP21, as a novel potent anti‐anaphylactic agent targeting platelet‐activating factor
A biotinylated peptide, BP21, as a novel potent anti‐anaphylactic agent targeting platelet‐activating factor
复制标题
生物素化肽 BP21，作为一种针对血小板激活因子的新型有效抗过敏剂
作者：
A. Sato;K. Ebina
血小板活化因子（PAF）是过敏反应的重要介质，因此是抗过敏药物的靶点。我们最近报道了合成的N-末端生物素化肽（BP 4-BP 29）通过与PAF及其代谢物/前体lyso-PAF直接相互作用来抑制PAF。在这项研究中，我们研究了生物素化肽是否可以抑制过敏反应在体内。在小鼠过敏反应模型中，其中一种肽BP 21可显著且剂量依赖性地抑制体温过低，在给药后30 min内达到最大剂量反应，即使剂量比已知PAF拮抗剂CV-3988低20倍。相比之下，其中BP 21中的Tyr-Lys-Asp-Gly序列被修饰为Gly-Gly-Gly-Gly序列的BGP 21的抗低温作用小于BP 21的抗低温作用。丙氨酸扫描和改组BP 4（Tyr-Lys-Asp-Gly）的氨基酸残基证明Tyr-Lys-Asp-Gly共有序列对于肽对体温过低的抑制作用是重要的。BP 21还在过敏反应期间抑制血管通透性，在给药后30分钟内具有最大剂量反应。在大鼠后爪水肿模型中，BP 21显著抑制PAF诱导的水肿，但不抑制其他促炎介质（如组胺、5-羟色胺和缓激肽）诱导的水肿。色氨酸荧光测定表明，BP 21与PAF相互作用，但不与组胺，5-羟色胺，缓激肽。BGP 21与PAF无相互作用。这些结果表明，生物素化肽，尤其是BP 21，可以特异性和显著地抑制体内过敏反应，这涉及其Tyr-Lys-Asp-Gly区与PAF的直接相互作用。因此，生物素化肽BP 21可用作靶向PAF的新型潜在抗过敏药物。Copyright © 2017 European Peptide Society and John Wiley & Sons，Ltd.
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.
DOI：
10.1152/ajpendo.00475.2009
发表时间：
2009-12-01
影响因子：
5.1
作者：
Cheng, Long;Han, Xiao;Shi, Yuguang
通讯作者：
Shi, Yuguang