期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-34793-6
关键词
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资金
- Asociacion Espanola contra el Cancer [POSTD211371MATE]
- MINECO [PRE2018-084684, PID2020-119810RB-I00, BIO2015-70092-R, PID2019-110198RBI00]
- Spanish Ministry of Science, Innovation [RYC2018-024759-I]
- AGAUR [2017 SGR 324]
- European Research Council (CONCERT) [648201]
- Novo Nordisk Foundation [NNF18OC0033926]
- Instituto Nacional de Bioinformatica
- EU BioExcel Centre of Excellence for HPC
- Spanish Ministry of Science [PID2021-122478NB-I00]
- Instituto de Salud Carlos III-Instituto Nacional de Bioinformatica - (Fondo Europeo de Desarrollo Regional) [ISCIII PT 17/0009/0007]
- Max Planck Society
- European Research Council (ERC) [648201] Funding Source: European Research Council (ERC)
This study presents design rules for creating peptides that fold into single alpha-helices by utilizing glutamine side chain to main chain hydrogen bonds. These peptides can be used to target globular proteins and have a wide range of applications.
The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into alpha-helices. These interactions offer opportunities for therapeutic intervention but their modulation with small molecules is challenging because they bury large surfaces. Linear peptides that display the residues that are key for binding can be targeted to globular proteins when they form stable helices, which in most cases requires their chemical modification. Here we present rules to design peptides that fold into single alpha-helices by instead concatenating glutamine side chain to main chain hydrogen bonds recently discovered in polyglutamine helices. The resulting peptides are uncharged, contain only natural amino acids, and their sequences can be optimized to interact with specific targets. Our results provide design rules to obtain single alpha-helices for a wide range of applications in protein engineering and drug design. Targeting biomedically relevant protein-protein interactions is a long-lasting challenge in medicinal chemistry. Here, the authors develop a single alpha-helical peptide scaffold that can be tailored to target globular proteins of biomedical interest.
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