SUPR Peptides to Inhibit Undruggable Cancer Target (PQ18)

SUPR 肽抑制无法药物治疗的癌症靶标 (PQ18)

基本信息

批准号：
8678709
负责人：
RICHARD W ROBERTS
金额：
$ 43.93万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
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/8678709
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

项目摘要

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（申请人提供）：本申请旨在证明扫描不自然的蛋白酶耐药性（SUPR）肽为靶向传统上不良蛋白质的问题提供了一种通用解决方案。为此，我们将使用具有扩展的遗传密码的mRNA显示器来创建一个高度稳定的膜 - 佩皮肽，可以阻止或调节两个最重要的细胞内蛋白质 - 蛋白质相互作用蛋白质赋予了致癌表型 - Ras和STAT3蛋白的活化形式。我们的三个具体目的是：1）设计靶向细胞内“不难”蛋白涉及癌症转化或维持的蛋白质的稳定的超肽，2）以表征并增强对癌症药物应用的选定上的肽功能，3）以评估体内特征和评估优化的肽药物治疗癌症治疗癌症的治疗潜力。总体而言，该项目旨在开发新的分子，以及一种靶向与癌症相关的蛋白质的一般方法，这些蛋白质已被证明是挑战性的，以至于蛋白质可以称为“不可用”。