The Nrf2/Keap1 interaction is a target in the development of new therapeutic agents, where inhibition of the interaction activates Nrf2 and leads to the generation of downstream anti-inflammatory effects. Peptides that mimic the β-turn in the Keap1 active site and are constrained by a disulfide bridge have high affinity for Keap1 but no intracellular activity. The introduction of a perfluoroalkyl-bridging group to constrain the peptides, coupled with a glutamic acid to proline replacement leads to a new peptide with a K_i of 6.1 nM for the Nrf2/Keap1 binding interaction, although this does not translate into intracellular activity.

中文翻译：

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基于全氟芳烃的肽大环化合物，可抑制Nrf2 / Keap1相互作用

Nrf2 / Keap1相互作用是新治疗剂开发的目标，其中相互作用的抑制激活Nrf2并导致下游抗炎作用的产生。模仿Keap1活性位点中的β-转角并受二硫键限制的肽对Keap1具有高亲和力，但没有细胞内活性。引入全氟烷基桥接基团以限制肽，再加上谷氨酸取代脯氨酸，可得到一种新的肽，其Nrf2 / Keap1结合相互作用的K _i为6.1 nM，尽管这并不转化为细胞内活性。