Development of Neutrophile Regulatory Peptides with Receptor Association Structures

具有受体缔合结构的中性粒细胞调节肽的开发

基本信息

批准号：
18550154
负责人：
KODAMA Hiroaki
金额：
$ 2.64万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Neutrophil functions including chemotaxis, degranulation, and generation of superoxide anion are modulated by diverse extracellular agonists such as N-formyl-methionyl-leucyl-phenylalanine (fMLP). Formyl peptide receptor (FPR) and formyl peptide receptor-like 1 (FPRL1), a superfamily of seven transmembrane (TM) proteins, are expressed on human neutrophils as the fMLP binding receptors. We found that human neutrophils pretreated with human formyl peptide receptor transmembrane (hFPRTM) peptides were enhanced superoxide anion production when stimulated with fMLP. However, a membrane protein interacting with hFPRTM peptides is not identified. To explore the sequence dependences of the TM peptides for neutrophil proming activities, peptides possess the TM sequences of formyl peptide receptor (FPR), FPR like 1 receptor (FPRL1), and GABA receptor were synthesized by solid-phase method with Fmoc chemistry. Homogeneities and structures of synthetic peptides were confirmed by HPLC and MALDI-TOF MS. The biological activities of synthetic peptides were carried out as superoxide production for human neutrophils. Neutrophils treated with TM peptides from FPR and FPRL1 produced 2-3 folds of superoxide anion by the treatment of fMLP, neutrophil agonist. TM peptide from GABA receptor exhibited no significant priming activity. These results suggested the priming effect of TM peptide for neutrophil was sequence dependence and it required the FPR related sequences.

中性粒细胞的功能，包括趋化性、脱颗粒和超氧阴离子的产生，受到多种细胞外激动剂的调节，例如 N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸 (fMLP)。甲酰肽受体 (FPR) 和甲酰肽受体样 1 (FPRL1) 是七种跨膜 (TM) 蛋白的超家族，在人中性粒细胞上表达为 fMLP 结合受体。我们发现，用人甲酰基肽受体跨膜 (hFPRTM) 肽预处理的人中性粒细胞在用 fMLP 刺激时，超氧阴离子的产生增强。然而，尚未鉴定出与 hFPRTM 肽相互作用的膜蛋白。为了探索TM肽对中性粒细胞促进活性的序列依赖性，通过Fmoc化学固相法合成了具有甲酰基肽受体（FPR）、FPR样1受体（FPRL1）和GABA受体TM序列的肽。通过 HPLC 和 MALDI-TOF MS 证实了合成肽的均质性和结构。合成肽的生物活性是通过人中性粒细胞产生超氧化物来实现的。用 FPR 和 FPRL1 的 TM 肽处理的中性粒细胞产生的超氧阴离子是 fMLP（中性粒细胞激动剂）处理的 2-3 倍。来自GABA受体的TM肽没有表现出显着的引发活性。这些结果表明TM肽对中性粒细胞的启动作用是序列依赖性的，并且需要FPR相关序列。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia

抗癌药物与纤连蛋白FNIII14肽联合治疗有效克服细胞粘附介导的急性髓系白血病耐药

DOI：
发表时间：
2008
期刊：
影响因子：
0
作者：
T.Matsunaga; F.Fukai; S.Miura; Y.Nakane; T.Owaki; H.Kodama; T.Nagaya; R.Takimoto; T.Takayama; Y.Niitsu
通讯作者：
Y.Niitsu

Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia

抗癌药物与纤连蛋白FNIII14肽联合治疗有效克服细胞粘附介导的急性髓系白血病耐药

DOI：
发表时间：
2008
期刊：
影响因子：
0
作者：
T.; Matsunaga; F.; Fukai; S.; Miura; Y.; Nakane; T.; Owaki; H.; Kodama; M.; Tanaka; T.; Nagaya; R.; Takimoto; T.; Takayama; Y.; Niitsu
通讯作者：
Niitsu

Ion-channel formation assisted by electrostatic interhelical interaction in covalently dimerized amphiphilic helical peptides

共价二聚两亲性螺旋肽中静电螺旋间相互作用辅助离子通道形成