SUPR Peptides to Inhibit Undruggable Cancer Target (PQ18)

SUPR 肽抑制无法药物治疗的癌症靶标 (PQ18)

• 批准号: 8546321
• 负责人: RICHARD W ROBERTS
• 金额: $ 43.4万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-17 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546321
• 关键词: Address; Affinity; Amino Acids; Antibodies; Antineoplastic Agents; Antitumor Response; Applications Grants; Binding; Biological; Biological Availability; C-terminal; Cell Culture Techniques; Cell Membrane Permeability; Cellular Membrane; Characteristics; Chemicals; Cyclic Peptides; Development; Dose; Drug resistance; Enzymes; Exhibits; Genes; Genetic Code; Goals; Guanosine Triphosphate; Human; Immune response; Immunosuppression; Libraries; Maintenance; Malignant Neoplasms; Malignant neoplasm of pancreas; Membrane; Membrane Proteins; Messenger RNA; Modification; Mus; Mutate; N Domain; Nucleotides; Oncogenic; Oral; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Phenotype; Play; Property; Proteins; Reagent; Resistance; Role; Route; Scanning; Serum; Solutions; Specificity; Stat3 protein; Testing; Therapeutic; Time; base; cancer cell; cancer immunotherapy; cancer therapy; cell growth; design; drug candidate; drug discovery; improved; in vivo; insight; mouse model; new technology; novel; nucleotide analog; originality; outcome forecast; pre-clinical; protein aminoacid sequence; protein farnesyltransferase; protein protein interaction; public health priorities; ras Proteins; response; src Homology Region 2 Domain; therapeutic target; tool; transcription factor; tumor

DESCRIPTION (provided by applicant): This application aims to demonstrate that Scanning Unnatural Protease Resistant (SUPR) peptides provide a general solution to the problem of targeting traditionally undruggable proteins. To do this, we will use mRNA display with an expanded genetic code to create a new class highly stabilized, membrane-permeant peptides that can block or modulate protein-protein interactions for two of the most important intracellular proteins conferring the oncogenic phenotype-the activated form of Ras and the Stat3 protein. Our three Specific Aims are: 1) To design stabilized SUPR peptides targeting intracellular "undruggable" proteins involved in cancer transformation or maintenance, 2) To characterize and enhance selected SUPR peptide functions towards cancer drug applications, and 3) To evaluate in vivo characteristics and assess the therapeutic potential of optimized SUPR peptide drug candidates for cancer treatment in mice. Overall, this project is intended to develop novel molecules as well as a general approach to target cancer-relevant proteins that have proved challenging up to this point-so much so that the proteins may be called "undruggable."

描述（由申请人提供）：本申请旨在证明扫描非天然蛋白酶抗性（SUPR）肽为靶向传统不可药物蛋白质的问题提供了一般解决方案。为了做到这一点，我们将使用mRNA展示和扩展的遗传密码来创建一类新的高度稳定的膜渗透肽，可以阻断或调节两种最重要的细胞内蛋白质-蛋白质相互作用