Shelterin是一个位于端粒末端的由六个蛋白形成的蛋白复合物，它的主要功能是保护染色体末端，避免它被DNA修复机制识别为DNA断裂。TRF2是Shelterin的重要组成部分，在3' DNA末端单链及T-loop的形成中都起着重要作用。敲落TRF2可以诱发DNA损伤修复机制。TRF2可以把很多其它蛋白招募到端粒上，这些蛋白也对保护端粒起着重要作用。在本项目中，根据从能与TRF2结合的蛋白Apollo中截取的多肽，我们设计了一系列TRF2的小分子抑制剂。这类化合物不仅能阻断TRF2与Apollo相互作用，还可以抑制TRF2对其它蛋白的招募。我们已经设计了有效的合成所设计的化合物的方法，在将来的工作中，我们将完成它们的合成并对它们的生理活性进行详细的表征。对这些化合物的研究，不仅将极大地丰富我们对端粒结合蛋白功能的了解，还有可能发现进行新药研究的新靶点。

TRF2 is a key member of Shelterin, a protein complex which locates at the end of telomere and plays an important role in the protection of telomere from being recognized as DNA damage.TRF2 plays an important role in the formation of T-loop and 3' single strand DNA overhang. Knockdown of TRF2 can induce DNA damage response. TRF2 can recruit many binding partners to telomere,which also play important roles in the protection of telomere. Among the proteins recruited by TRF2, Apollo is the most studied one. Apollo is a 5'-exo nuclease which contributes to the formation of 3' single strand DNA overhang in the leading strand replication and also plays an important role in DNA repair. In this project, based on a peptide from Apollo, we designed a series of small molecular compounds which can bind to TRF2 and block its interaction with its binding partners and thus function as inhibitors of TRF2. We have designed efficient synthetic methods for the synthesis of these compounds and will perform their synthesis and biochemical and biological evaluation in future work. Successfully carrying out, we will be able to identify potent TRF2 inhibitors which can be extensively used in telomere related studies. These studies will not only greatly enrich our knowledge in proteins associated with telomere, but will have the potential to identify new targets for the development of novel drugs for the treatment of human disease, including cancer.