期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 48, 页码 17351-17358出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201907901
关键词
constrained peptides; peptide inhibitors; protein structure; protein-DNA interactions; protein-protein interactions
资金
- Deutsche Forschungsgemeinschaft (DFG
- Emmy Noether program) [GR3592/2-1]
- European Reasearch Council (ERC) [678623]
- Regione Campania-POR Campania FESR 2014/2020 Combattere la resistenza tumorale: piattaforma integrata multidisciplinare per un approccio tecnologico innovativo alle oncoterapie-Campania Oncoterapie [B61G18000470007]
- Astra Zeneca
- Bayer CropScience
- Bayer Health-Care
- Boehringer Ingelheim
- Merck KGaA
- Max Planck Society
- European Research Council (ERC) [678623] Funding Source: European Research Council (ERC)
Protein complex formation depends on the interplay between preorganization and flexibility of the binding epitopes involved. The design of epitope mimetics typically focuses on stabilizing a particular bioactive conformation, often without considering conformational dynamics, which limits the potential of peptidomimetics against challenging targets such as transcription factors. We developed a peptide-derived inhibitor of the NF-Y transcription factor by first constraining the conformation of an epitope through hydrocarbon stapling and then fine-tuning its flexibility. In the initial set of constrained peptides, a single non-interacting alpha-methyl group was observed to have a detrimental effect on complex stability. Biophysical characterization revealed how this methyl group affects the conformation of the peptide in its bound state. Adaption of the methylation pattern resulted in a peptide that inhibits transcription factor assembly and subsequent recruitment to the target DNA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据