Chemical platform to produce covalent biologics

项目总结 拟议研究计划的目标是开发一种化学平台技术，以生产和 优化共价生物制剂--一种新的治疗方式。生物药物构成了药物的一大部分 然而，它们的缺点是价格高，需要频繁注射。我们假设 共价生物制剂将具有更高的效力，并且需要更少的频繁注射。传统的 生产共价生物制品的方法依赖于非天然氨基酸的诱变，但这种方法不是 产量下降，并受到蛋白质产量下降的影响。拟议中的化学技术旨在 通过提高共价生物产率来克服这些挑战，允许快速合成和测试100个 一天内共价生物药物，并允许几乎无限数量的共价弹头可以 安装在质膜表面。这是一个没有任何初步数据的高风险建议书，根据 PAR-19-254。我们的初步探索性研究将集中在开发化学平台和验证它 在基于细胞的研究中使用免疫检查点抑制剂和抗炎蛋白疗法 活着。这是休斯顿大学的Alexander Statsyuk参与的联合PI提案(专业知识 化学和蛋白质生物化学)和来自Prairie View A&M大学的Victoria Mgbemena(专业知识 免疫学和老鼠生物学)。草原景观农工大学属于历史悠久的黑人学院和 大学，并为在科学领域代表性不足的少数族裔学生群体提供服务。

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.