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Molecular mimicry of carbohydrate receptors and its application for the control of infectious diseases

碳水化合物受体的分子模拟及其在传染病控制中的应用

基本信息

批准号：
13556045
负责人：
OHASHI Kazuhiko
金额：
$ 8.96万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Many kinds of infectious agents, such as viruses and bacteria, invade target cells through their binding to carbohydrate receptors expressed on the target cell surfaces. Since their specificities to these carbohydrate receptors do not change even after these infectious agents undergo antigenic shift or mutations, it would be possible to use these carbohydrate receptors for the protection from these infectious diseases. However, the preparation of a large amount of carbohydrate receptors is technically difficult. Thus, in this study, using the New castle disease virus (NDV)-carbohydrate receptor (sialic acid) interaction as a model, a search for peptide surrogates which can mimic the carbohydrate structure of the receptor was performed, and their protective effcicacies were evaluated against NDV infection.Three individual peptide sequences, EVSHPKVG, WVTTSNQW and SGGSNRSP, which have potentials to bind to hemagglutinin-neuraminidase of NDV were identified by the biopanning method using phage display system. The binding specificities of these peptides presented on phages were confirmed by the ELISA competition assay using chicken antiserum to NDV. The synthetic peptides designed based on the results did not inhibit the hemagglutination by inactivated NDV, but partially neutralized the infection of NDV in vitro. In the future, it will be necessary to modify these peptides sequences, for example substitution of amino acids, to improve their abilities to bind to NDV and to inhibit NDV infection. It is also important to examine the protective efficacies of them against NDV in vivo for clinical application.

许多种类的感染因子，例如病毒和细菌，通过它们与靶细胞表面上表达的碳水化合物受体结合来侵入靶细胞。由于它们对这些碳水化合物受体的特异性即使在这些感染因子经历抗原性转变或突变后也不改变，因此有可能使用这些碳水化合物受体来保护免受这些感染性疾病。然而，制备大量的碳水化合物受体在技术上是困难的。因此，在本研究中，使用新城堡病病毒（NDV）-碳水化合物受体，（唾液酸）相互作用作为模型，进行了能够模拟受体的碳水化合物结构的肽替代物的搜索，并评估了它们对NDV感染的保护效果。利用噬菌体展示系统筛选出与新城疫病毒血凝素-神经氨酸酶结合的噬菌体。用鸡抗NDV血清进行ELISA竞争试验，证实了这些肽的结合特异性。在此基础上设计的合成肽对NDV灭活后的血凝反应无抑制作用，但对NDV的感染有部分中和作用。将来，有必要修饰这些肽序列，例如氨基酸的取代，以提高它们结合NDV和抑制NDV感染的能力。研究其体内抗新城疫病毒的保护效果对临床应用也有重要意义。