A glutamine-based single ¿-helix scaffold to target globular proteins.

The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-helices. These interactions offer opportunities for therapeutic intervention but their modulation with small molecules is challenging because they bury large surfaces. Linear peptides that disp...

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Detalles Bibliográficos
Autores: Escobedo, Albert, Piccirillo, Jonathan, Aranda, Juan, Diercks, Tammo, Mateos, Borja, Garcia-Cabau, Carla, Sánchez-Navarro, Macarena, Topal, Busra, Biesaga, Mateusz, Staby, Lasse, Kragelund, Birthe B., Millet, Oscar, Orozco, Modesto, Coles, Murray, Crehuet, Ramón, Salvatella, Xavier, García, Jesús
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/360259
Acceso en línea:http://hdl.handle.net/10261/360259
Access Level:acceso abierto
Descripción
Sumario:The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-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 α-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 α-helices for a wide range of applications in protein engineering and drug design.

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