Random aptamers to probe SCL function in vivo.

用于探测体内 SCL 功能的随机适体。

• 批准号: nhmrc : 211955
• 负责人: A/Pr Paul Watt
• 金额: $ 18.09万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/random-aptamers-probe-function-vivo/92329
• 关键词: Random; aptamers; probe; SCL; function

Modern chemotherapies are designed to exert maximal effect on tumour cells while having minimal side-effects on normal cells. Remarkable advances in our understanding of the molecular biology of cancer has provided possible avenues for more successful targeted cancer treatments. Several crucial interactions between cancer-specific proteins called oncoproteins , occur largely in tumour cells and thus provide ideal targets for intervention. The proposed project is to develop a model system for a target specific therapy of leukaemia cells by blocking the interactions between oncoproteins. Moreover, the ability to isolate specific blockers of particular protein-protein interactions provides an opportunity to unravel complex genetic pathways in mammalian systems, which are relatively intractable by other analyses. The dissection of pathways using specific blockers may also provide a useful avenue for identifying new drug targets. We have chosen to target particular interactions involving one known oncoprotein in the search for specific inhibitors. A genetic selection will be used to identify random, constrained peptide sequences which are capable of blocking these interactions and which do not interfere with other interactions involving the oncoprotein. This technique allows one to select for or against specific blockers of known interactions from a library containing millions of candidate drug leads in baker's yeast cells. This procedure will be most suitable for high through-put drug screening projects. The validity of this approach to the identification of new peptide drug leads will be finally established in vivo using transgenic models of oncoprotein-dependent cancer in mice.

现代化学疗法旨在对肿瘤细胞发挥最大的作用，同时对正常细胞产生最小的副作用。我们对癌症分子生物学的理解取得了显著进展，为更成功的靶向癌症治疗提供了可能的途径。被称为癌蛋白的癌症特异性蛋白之间的几种关键相互作用主要发生在肿瘤细胞中，因此为干预提供了理想的目标。提出的项目是通过阻断癌蛋白之间的相互作用来开发白血病细胞靶向特异性治疗的模型系统。此外，分离特定蛋白质-蛋白质相互作用的特异性阻滞剂的能力为揭示哺乳动物系统中复杂的遗传途径提供了机会，这是其他分析相对难以解决的。利用特异性阻滞剂解剖通路也可能为鉴定新的药物靶点提供有用的途径。我们在寻找特异性抑制剂时选择了涉及一种已知癌蛋白的特定相互作用。基因选择将用于识别随机的、受限的肽序列，这些序列能够阻断这些相互作用，并且不会干扰涉及癌蛋白的其他相互作用。这项技术允许人们从面包师酵母细胞中含有数百万候选药物先导物的文库中选择或反对已知相互作用的特定阻滞剂。本程序最适用于高通量药物筛选项目。这种方法在鉴定新肽药物先导物方面的有效性最终将在体内利用癌蛋白依赖的小鼠癌症转基因模型得到验证。