中药蟾蜍分泌物中的抗癌活性多肽的发现及其机制研究

As a traditional Chinese medicinal material, Chansu is the dry product of toad skin secretion. Many research have reported that toad skin and its secretions demonstrated with high pharmaceutical diversities due to the bioactive peptides in it. Due to their relative specific targets and tiny side effects, some peptide-based drugs have successfully gone into the market and achieved good market efficiency and positive social value. However, the peptide-based drugs were rarely studied before, since the discovery of their sequences and determination of their characteristics were complex and time consuming. Hence, in this project, we firstly set up a high throughput screening platform to construct the toad skin section peptide library through combining transcriptoms and proteomes, which is more efficient and lower cost. Based on transcriptoms and proteomes, we have already successfully constructed a toad skin section peptide library by bioinformatics analysis, and isolated a panel of potential novel anticancer peptides. Another reason why peptide-based drugs is scarce is that the mechanism was rarely studied and still unclear for now. Hence, in this project, we proposed to further study the anticancer mechanisms of those potential novel anticancer peptides to proceed them into pre-clinical trials. Besides this, we also proposed to construct the construction-function relationships of the toad skin section peptide library, in order to modify the anticancer peptides to enhance their bioactivities and reduce their side effects, which could promote the current drug discovery and cancer treatment.

作为传统中药材，蟾酥主要是蟾蜍皮肤分泌物的干燥产物。许多研究表明，蟾蜍皮肤分泌物含有多种有效活性成分，其中又以活性多肽为其主要成分之一。基于多肽类药物活性作用强、毒副作用低、且能克服耐药性的特点，开发研究多肽类药物成为新型抗肿瘤药物成为目前研究的热点。然而由于提取鉴定多肽序列和相关特性十分繁复和耗时，目前市场上的多肽类药物很缺乏。因此我们在本项目中创新性地提出建立高通量筛选平台，通过结合基因组学和蛋白组学，在组学层面上运用生物信息学去最大程度地分析蟾蜍分泌物活性多肽的成分，最大程度地提高了研究效率并降低了研究成本。基于此高通量筛选平台，课题组前期建立了蟾蜍分泌物的多肽文库，并筛选出了多个新型潜在活性抗癌多肽。市场上多肽类药物的缺乏另一个主要因素即是对其活性作用机制的研究很匮乏，因此我们将深入研究前期发现的新型抗癌多肽的活性作用及作用机制，这对推进多肽药物发展具有重要的意义。此外，我们将通过

作为传统中药材，蟾酥主要是蟾蜍皮肤分泌物的干燥产物。许多研究表明，蟾蜍皮肤分泌物含有多种有效活性成分，其中又以活性多肽为其主要成分之一。基于多肽类药物活性作用强、毒副作用低、且能克服耐药性的特点，开发研究多肽类药物成为新型抗肿瘤药物成为目前研究的热点。然而由于提取鉴定多肽序列和相关特性十分繁复和耗时，目前市场上的多肽类药物很缺乏。因此我们在本项目中创新性地提出建立高通量筛选平台，通过结合基因组学和蛋白组学，在组学层面上运用生物信息学去最大程度地分析蟾蜍分泌物活性多肽的成分，最大程度地提高了研究效率并降低了研究成本。基于此高通量筛选平台，课题组前期建立了蟾蜍分泌物的多肽文库，并筛选出了多个新型潜在活性抗癌多肽。市场上多肽类药物的缺乏另一个主要因素即是对其活性作用机制的研究很匮乏，因此我们将深入研究前期发现的新型抗癌多肽的活性作用及作用机制，这对推进多肽药物发展具有重要的意义。此外，我们将通过建立多肽文库的构效关系对潜在抗癌多肽进行修饰改造，从而推进新药研发和新型癌症疗法。