BioCIS, Univ. Paris-Sud, CNRS, Université Paris Saclay, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France.
BioCIS, Univ. Paris-Sud, CNRS, Université Paris Saclay, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France.
Curr Opin Chem Biol. 2019 Oct;52:157-167. doi: 10.1016/j.cbpa.2019.07.008. Epub 2019 Oct 4.
Protein-protein interactions involving β-sheet secondary structures have been questioned in many fatal human diseases such as cancer, autoimmune and neurodegenerative diseases. Small selective peptide derivatives and analogues are promising drug candidates for inhibiting this poorly known class of PPIs. In this review, we will highlight the main strategies developed for designing linear and cyclic peptide and peptidomimetic inhibitors of PPIs involving β-sheet structures. These compounds either do not adopt preferred conformations or can mimic protein secondary structures such as β-strands, β-hairpins or α-helices.
涉及β-折叠二级结构的蛋白质-蛋白质相互作用已在许多致命的人类疾病中受到质疑,如癌症、自身免疫性和神经退行性疾病。小的选择性肽衍生物和类似物是抑制这种鲜为人知的蛋白质-蛋白质相互作用类别的有前途的药物候选物。在这篇综述中,我们将重点介绍为设计涉及β-折叠结构的蛋白质-蛋白质相互作用的线性和环状肽和肽模拟物抑制剂而开发的主要策略。这些化合物要么不采用首选构象,要么可以模拟蛋白质二级结构,如β-链、β-发夹或α-螺旋。