Molecule-Guided Investigations into p53 Biology

p53 生物学的分子引导研究

• 批准号: 8175349
• 负责人: Federico Bernal
• 金额: $ 69.45万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8175349
• 关键词: Apoptosis; Attention; Behavior; Binding Sites; Biochemical; Biochemistry; Biological; Biological Assay; Biology; Cancer cell line; Cell Cycle Arrest; Cell physiology; Cells; Cellular biology; Charge; DNA Damage; DNA Repair; Deletion Mutation; Development; Ensure; Equipment; Evaluation; Genetic Transcription; Genome; Goals; Homeostasis; Housing; Investigation; Laboratories; MDM2 gene; Malignant Neoplasms; Molecular Biology; Mus; Nuclear Receptors; Pathway interactions; Peptides; Play; Positioning Attribute; Property; Protein Binding; Protein p53; Proteins; Recombinant Proteins; Research; Research Infrastructure; Role; Signal Transduction; Starvation; Synthesis Chemistry; System; TP53 gene; Testing; Therapeutic; Time; Transcriptional Activation; Tumor Suppressor Proteins; Variant; Work; alpha helix; cancer cell; design; liquid chromatography mass spectrometry; programs; restoration; transcription factor

The setup of the Bernal Laboratory began in May of 2010. Over the course of the last few months, we have been dedicating our time to build the infrastructure of the laboratory. Now that the renovations and construction of the lab space has been completed and most of the equipment has been installed, we are poised to embark in the investigations outlined above. The work in this project is multi-disciplinary, and it comprises a mixture of synthetic chemistry, biochemistry, molecular biology and cell biology. With the recent installation of a peptide synthesizer and a liquid chromatography mass spectrometry (LC/MS) system in my laboratory, we are prepared to design, synthesize and purify the stapled peptides that we will use in our biological studies. We currently aim to construct compounds that include the murine variants of SAH-p53 (see Goals section), modulators of RING domain interactions in proteins involved in ubiquitylation, and peptides that block the activation function and coactivator binding site of nuclear receptors. On the biology front, we will be well-positioned to study in-house all of the molecules that we will synthesize in the laboratory. We will explore the biochemical and biophysical properties of the compounds and test their behavior in protein binding assays. Their activity will be assessed using both recombinant proteins and a wide array of cancer cell lines.

Bernal实验室的设置始于2010年5月。在过去的几个月中，我们一直在努力建立实验室的基础设施。现在，已经完成了实验室空间的翻新和建设，并且已经安装了大多数设备，我们已经准备好开始上面概述的调查。 该项目的工作是多学科的，它包括合成化学，生物化学，分子生物学和细胞生物学的混合物。随着肽合成器的最新安装和我的实验室中液相色谱质谱（LC/MS）系统，我们准备在生物学研究中设计，合成和净化钉钉肽。我们目前的目标是构建包括SAH-P53的鼠变体的化合物（请参见目标部分），参与泛素化蛋白质中的环域相互作用的调节剂以及阻断激活函数的肽和核受体结合位点的肽。 在生物学方面，我们将有充分的位置研究我们将在实验室中合成的所有分子。我们将探索化合物的生化和生物物理特性，并测试其在蛋白质结合测定中的行为。它们的活性将使用重组蛋白和多种癌细胞系进行评估。