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类肽作为天然活性肽的结构或功能模拟物,具有3个优点:一是能够保留天然肽的底物功能,二是可改善其代谢性质,三是可提高其作用的靶向专一性等特点.高活性的类肽分子设计可通过构象限定、结构改造和非肽模拟物设计的构思等多种手段实现.目前肿瘤化疗药物开发的研究热点已由细胞毒药物转向靶向治疗药物,在肿瘤发生发展过程中起关键作用的许多蛋白酶和肽酶陆续被发现,因此类肽作为潜在的肿瘤化疗药物已倍受关注,而如何设计具有抗肿瘤活性的小分子类肽酶抑制剂则已成为研究的热点.本课题组多年来一直致力于研究开发APN、MMPs及HDACs的小分子类肽抑制剂作为靶向抗肿瘤药物先导物.这三种锌离子依赖性金属蛋白酶在肿瘤的生长侵袭转移、血管生成和基质降解等发展进程中起着关键作用,靶向于该类生物靶点的小分子类肽抑制剂具有开发成为高选择性抗肿瘤药物的巨大潜力.
Peptides, as structural or functional mimics of naturally-occurring peptides, have three advantages: one is the ability to retain the substrate function of the native peptide, the other is to improve their metabolic properties and the third is the specificity of targeting that can enhance their effect The design of highly active peptoid molecules can be achieved through conformational restriction, structural modification and the concept of non-peptidomimetic design etc. At present, the research hotspot in the development of chemotherapeutic drugs has turned from cytotoxic drugs to targeted therapies, Many proteases and peptidases that play key roles in the development of tumors have been discovered one after another, and therefore, peptoids have drawn much attention as potential tumor chemotherapeutic drugs. How to design small-molecule peptidase inhibitors with anti-tumor activity has become Research hot.Our group has been committed to the research and development of APN, MMPs and HDACs of small peptide inhibitors as a targeted anti-tumor drug lead .The three zinc ion-dependent metalloproteinases in tumor growth invasion and metastasis , Angiogenesis and stromal degradation plays a key role in the development process, targeted to such biological targets of small peptide inhibitors have developed into a high election Selective antitumor drugs have great potential.