Sang Peng, Shi Yan, Higbee Pirada, Wang Minghui, Abdulkadir Sami, Lu Junhao, Daughdrill Gary, Chen Jiandong, Cai Jianfeng
Department of Chemistry, University of South Florida, 4202 E. Fowler Ave., Tampa, Florida 33620, United States.
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida 33620, United States.
J Org Chem. 2020 Aug 21;85(16):10552-10560. doi: 10.1021/acs.joc.0c00996. Epub 2020 Aug 2.
Novel unprecedented helical foldamers have been effectively designed and synthesized. The homogeneous right-handed d-sulfono-γ-AApeptides represent a new generation of unnatural helical peptidomimetics, which have similar folding conformation to α-peptides, making them an ideal molecular scaffold to design α-helical mimetics. As demonstrated with p53-MDM2 PPI as a model application, the right-handed d-sulfono-γ-AApeptides reveal much-enhanced binding affinity compared to the p53 peptide. The design of d-sulfono-γ-AApeptides may provide a new and alternative strategy to modulate protein-protein interactions.
新型前所未有的螺旋折叠体已被有效设计与合成。均一的右旋d-磺基-γ-氨基酸肽代表了新一代非天然螺旋肽模拟物，其具有与α-肽相似的折叠构象，使其成为设计α-螺旋模拟物的理想分子支架。以p53-MDM2蛋白-蛋白相互作用作为模型应用表明，与p53肽相比，右旋d-磺基-γ-氨基酸肽显示出显著增强的结合亲和力。d-磺基-γ-氨基酸肽的设计可能为调节蛋白-蛋白相互作用提供一种新的替代策略。
