Cyclic Peptidic Mimetics of Apollo Peptides Targeting Telomeric Repeat Binding Factor 2 (TRF2) and Apollo Interaction
Cyclic Peptidic Mimetics of Apollo Peptides Targeting Telomeric Repeat Binding Factor 2 (TRF2) and Apollo Interaction
复制标题
靶向端粒重复结合因子 2 (TRF2) 的 Apollo 肽的环状肽模拟物和 Apollo 相互作用
DOI：
10.1021/acsmedchemlett.8b00152
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发表时间：
2018-05-01
影响因子：
4.2
通讯作者：
Wang, Shaomeng
中科院分区：
文献类型：
--
作者：
Chen, Xia;Liu, Liu;Wang, Shaomeng
端粒重复序列结合因子2（Telomericrepeatbindingfactor 2，TRF 2）是一种端粒相关蛋白，它在3'端单链DNA突出端和“T环”的形成中起重要作用，这两种结构对端粒的稳定性至关重要。Apollo是由TRF 2募集到端粒的5 '-外切核酸酶，并有助于3'单链DNA突出端的形成。敲低Apollo基因可诱导类似于敲低TRF 2基因的DNA损伤反应。在这封信中，我们报告的设计和合成的一类环状肽模拟物的TRFH结合基序的阿波罗（阿波罗（TBM））。我们发现对Apollo（TBM）的C末端残基进行构象控制可以有效地提高结合亲和力。我们已经获得了与TRF 2复合的环状肽Apollo肽模拟物（34）的晶体结构，这为未来设计TRF 2抑制剂提供了有价值的指导。
Telomeric repeat binding factor 2 (TRF2) is a telomere-associated protein that plays an important role in the formation of the 3' single strand DNA overhang and the "T loop", two structures critical for the stability of the telomeres. Apollo is a 5'-exonuclease recruited by TRF2 to the telomere and contributes to the formation of the 3' single strand DNA overhang. Knocking down of Apollo can induce DNA damage response similar to that caused by the knocking down of TRF2. In this Letter, we report the design and synthesis of a class of cyclic peptidic mimetics of the TRFH binding motif of Apollo (Apollo(TBM)). We found conformational control of the C terminal residues of Apollo(TBM) can effectively improve the binding affinity. We have obtained a crystal structure of a cyclic peptidic Apollo peptide mimetic (34) complexed with TRF2, which provides valuable guidance to the future design of TRF2 inhibitors.