Chemical platform to produce covalent biologics

生产共价生物制剂的化学平台

基本信息

批准号：
10688088
负责人：
Alexander V Statsyuk
金额：
$ 18.34万
依托单位：
UNIVERSITY OF HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10688088
关键词：
Address Amino Acyl-tRNA Synthetases Anti-Inflammatory Agents Antibodies Biological Biological Assay Biological Models Biological Products Biological Response Modifier Therapy Biology Cells Chemicals Chemistry Cysteine Data Engineering Future Historically Black Colleges and Universities Hormones Immune checkpoint inhibitor Immunoglobulin Fragments Immunology In Vitro Injections Instruction Insulin KRAS2 gene Knowledge Literature Metabolic Methods Modality Monoclonal Antibodies Mus Mutagenesis Nature Pharmaceutical Preparations Population Positioning Attribute Price Production Protein Biochemistry Proteins Ras Inhibitor Reaction Reporting Research Science Structure-Activity Relationship Students Surface System Technology Testing Therapeutic Therapeutic Uses Transfer RNA Translating Underrepresented Minority Universities Work anakinra analog clinical candidate covalent bond crosslink drug discovery high risk high throughput screening human disease improved in vivo new technology novel therapeutics pharmacologic prevent programmed cell death protein 1 programs protein aggregation protein crosslink public health relevance receptor screening small molecule technology platform therapeutic cytokines therapeutic protein unnatural amino acids virtual

项目摘要

PROJECT SUMMARY The objective of the proposed research program is to develop a chemical platform technology to produce and optimize covalent biologics - a new therapeutic modality. Biologic drugs constitute the large sector of drug discovery, however their downside is a high price and the need for frequent injections. We hypothesize that covalent biologics will have much higher potency and will need less frequent injections. The conventional methods to produce covalent biologics rely on unnatural aminoacid mutagenesis but this method is not throughput and suffer from the reduced protein production yields. The proposed chemical technology aims to overcome these challenges by improving covalent biologic yield, allowing rapid synthesis and testing of 100s of covalent biologic drugs in one day, and allowing virtually unlimited number of covalent warheads that can be installed on the protien surface. This is a high risk proposal without any preliminary data as per instructions in PAR-19-254. Our initial exploratory studies will focus on developing the chemical platform and validating it using immune checkpoint inhibitors and anti-inflammatory protein therapeutics in both cell based studies and in vivo. This is a Co-PI proposal involving Alexander Statsyuk from the University of Houston (expertise in chemistry and protein biochemistry) and Victoria Mgbemena from the Prairie View A&M University (expertise in immunology and mouse biology). Prairie View A&M University belongs to historically black colleges and universities, and serves student population who are underrepresented minorities in science.

项目摘要拟议的研究计划的目的是开发一种化学平台技术来生产和优化共价生物制剂 - 一种新的治疗方式。生物药物构成大型药物发现，但是他们的缺点是高价，并且需要经常注射。我们假设这一点共价生物制剂将具有更高的效力，并且需要较少的注射频率。传统生产共价生物制剂的方法依赖于非天然氨基酸诱变，但该方法不是吞吐量和蛋白质产量降低。提出的化学技术旨在通过改善共价生物产量来克服这些挑战，从而快速合成和测试100s 有一天的共价生物药物，并允许几乎无限的共价弹头安装在蛋白表面上。这是一个高风险提案，没有任何初步数据 Par-19-254。我们最初的探索性研究将着重于开发化学平台并验证它在基于细胞的研究和IN中，使用免疫检查点抑制剂和抗炎蛋白治疗剂体内。这是一个涉及休斯顿大学亚历山大·斯塔西克（Alexander Statsyuk）的共同提案（专业知识化学和蛋白质生物化学）和Prairie View A＆M University的Victoria Mgbemena（专业知识免疫学和小鼠生物学）。大草原观点A＆M大学属于历史上的黑人大学，大学，为科学人数不足的学生人数提供服务。