SYNTHETIC BZIP PROTEINS AS TARGETING AGENTS FOR PDT

合成 BZIP 蛋白作为 PDT 靶向药物

基本信息

批准号：
6028232
负责人：
MICHAEL Y OGAWA
金额：
$ 9.09万
依托单位：
BOWLING GREEN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-05-01 至 2003-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6028232
关键词：
DNA binding protein drug delivery systems gel mobility shift assay intracellular transport metal complex metalloproteins neoplasm /cancer photoradiation therapy nucleic acid sequence peptide chemical synthesis synthetic protein transcription factor transport proteins

项目摘要

The following proposal for a NIH-AREA grant describes a pilot study designed to test the efficacy of utilizing the family of bZIP transcription factors to target photodynamic therapy (PDT) reagents to specific sequences of DNA (i.e. the AP-1 element: 5'-TGAGTCA-3'). In particular, both native and de novo designed bZIP proteins will be derivatized with photoactive metal complexes which have been previously shown to cause DNA damage by either direct photoinduced electron-transfer and/or the photochemical generation of singlet oxygen (1O2). The in vitro DNA recognition properties of these metallopeptides will then be studied by electrophoretic mobility shift assays, as will be their ability to produce site-specific DNA photodamage. Transient absorption and emission lifetime studies will be conducted on these systems to help identify the mechanisms involved in the photolesion process. An advantage in using bZIP proteins as targeting vehicles for PDT reagents is that their recognition elements can be found within a large number of promoters which participate in such important processes as cell differentiation and proliferation. Damage to these sites should be very cytotoxic. An additional advantage in the proposed approach to deliver PDT drugs to specific intracellular targets is that it can, in principle, be used to deliver a wide variety of PDT drugs. It is believed that the work described in this proposal will provide a new opportunity for students at Bowling Green State University to participate in a multi-disciplinary research project which may encourage their interest in pursuing graduate studies in the biomedical sciences. Receipt of this award will also enhance the PI's ability to pursue the goals of this focused pilot-project.

NIH-Area赠款的以下提案描述了一项试点研究，旨在测试利用BZIP转录因子家族来靶向光动力疗法（PDT）试剂对DNA的特定序列（即AP-1元素：5'-tgagtca-3'）的功效。特别是，天然和从头设计的BZIP蛋白都将被光活性金属配合物衍生而来，这些金属复合物先前已被证明会通过直接光诱导的电子转移和/或单粒氧的光化学产生（1O2）引起DNA损伤。这些金属肽的体外DNA识别特性将通过电泳迁移率分析研究，这将是产生位点特异性DNA光损伤的能力。瞬态吸收和排放寿命研究将在这些系统上进行，以帮助确定光子过程中涉及的机制。使用BZIP蛋白作为PDT试剂的靶向车辆的优势是，它们的识别元素可以在参与细胞分化和增殖等重要过程的大量启动子中找到。对这些部位的损害应非常细胞毒性。在提议的方法向特定细胞内靶标输送PDT药物的方法中，它原则上可以用于提供多种PDT药物。据信，该提案中描述的工作将为鲍灵格林州立大学的学生提供一个新的机会，参加了一个多学科研究项目，这可能会鼓励他们兴趣从事生物医学科学的研究生学习。该奖项的收到还将增强PI追求这一重点的试点项目的目标的能力。