该申请对应指南中的研究重点“发展和建立调控生物大分子动态修饰的小分子新工具、新策略，重点关注针对参与生物大分子动态修饰的靶酶，发展集中DNA编码分子库（Focus DNA-encoded library）构建和筛选技术体系，并在本重大研究计划中推广使用，用于干预生物大分子动态修饰化学分子的发现”。如何发现干扰大分子动态修饰的小分子是大分子动态修饰的化学干预的基本问题。核酸编码化合物库筛选平台可以为大分子找到有效的小分子化学探针。本项目利用有限的资源设计和合成聚焦的核酸编码化合物库，并“共享”来支持学术界对大分子靶酶的筛选来快速找到活性小分子，促进对大分子动态修饰的化学干预和进一步的靶点确认和药物开发。本项目提出建立共享的聚焦的核酸编码化合物库可以缓解目前我们国家大的化合物库匮乏的基本国情，可以以低成本有力的支持学术界的大规模筛选研究, 为本重大研究计划的更好完成提供有力的技术支持。

This application follows the guidance of the research focus, that is, “the development and establishment of novel small molecule tools and strategies for regulating the dynamic modification of biomacromolecules, focusing on dynamic modification of biomacromolecules target enzymes, and developing Focus DNA- Encoded library synthesis and screening technologies for its application in the discovery of biomolecules dynamically modifying chemical molecules inside the major research projects". How to identify small molecules that interfere with the dynamic modification of macromolecules target enzymes is the fundamental problem of chemical intervention of macromolecular dynamic modification. The DNA encoded chemical library platform is an effective method to find the small molecule chemical probes for macromolecule targets. This proposal applied limited budget to design and synthesize focused DNA encoded libraries and “shared” to support academic research group for screening macromolecular target enzymes, which was expected to quickly find active small molecules and promote chemical interventions for macromolecular dynamic modification as well as further target validation and drug development. This proposal proposed to establish a “shared” focused DNA encoded library to alleviate the current situation of large compound library shortage in our country, and to support large-scale compound library screening research in academia at low cost, which could provide strong technical support for the better completion of major research projects.