牛蛙凝集素受体及其药物靶向载体的初步研究

项目名称： 牛蛙凝集素受体及其药物靶向载体的初步研究

项目编号： No.31201886

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 畜牧学与草地科学、兽医学、水产学

项目作者： 赵瑞利

作者单位： 天津农学院

项目金额： 21万元

中文摘要： 凝集素具有对某一种特异性糖基专一性结合的能力，生物体不同的器官与组织含有不同的糖基，凝集素可以专一地与不同的器官或组织相结合，因此凝集素可以作为研究细胞膜结构的探针、药物靶向输送和定位的载体。目前已知的凝集素分子量都大于10KD，且从两栖动物中发现的凝集素非常有限。本研究通过筛选牛蛙皮肤cDNA文库得到分子量为1470的牛蛙凝集素Catesbeianalectin，多肽合成牛蛙凝集素，测定其对红细胞及临床常见致病菌的凝集活性。圆二色谱测定不同溶液环境对多肽结构的影响，并利用表面等离子共振（SPR）筛选出与牛蛙凝集素特异性结合的糖基配体，确定其分子结构。体内试验以同位素示踪法检测牛蛙凝集素在小鼠体内的稳定性及组织专一性，以牛蛙凝集素为基础的药物设计阻断病原体对受体细胞的粘着与药物靶向提供初步的理论基础。

中文关键词： 牛蛙凝集素；免疫原性；表面等离子共振；放射性标记；靶向载体

英文摘要： Lectins are sugar-binding proteins that specifically recognize sugar complexes.Based on the specificity of protein-sugar interactions,different lectins could be used as carrier molecules to target drugs specifically to different cells which express different glycan arrays. In spite of lectin interesting biological potential for drug targeting and delivery,a potential disadvantage of natural lectins may be large size molecules than 10KD. A lectin-like peptide named catesbeianalectin was identified from the cDNA library of rana catesbeiana. Erythrocyte agglutination activity detection showed that a lectin of Rana catesbeiana with the molecular weight of 1470, which is smaller than any other known lectin from amphibian, has very low homology with the other lectin. catesbeianalectin had very high rabbit erythrocyte agglutination activity with the minimum concentration 12.5μg/mL. It was also indicated that it had significant bacterial agglutination activity by laser scanning confocal microscope for Staphyloccocus aureus, streptococcus suis, Salmonella, Actinobacillus pleuropneu moniae.the small size and single disulfide bridge of catesbeianalectin make it easy to manipulate for developing as drug targeting system.Its structure and function were studied by SPR,125I-catesbeianalectin was stable in mice plasma.these f

英文关键词： Catesbeianalectin；Immunogenicity；SPRi；Radiolabelling；Targeting carrier