On the scope of the double Ugi multicomponent stapling to produce helical peptides

• Published in: Bioorganic chemistry 2021-08, Vol.113, p.104987-104987, Article 104987
• Main Authors: Ricardo, Manuel G., Vázquéz-Mena, Yadiel, Iglesias-Morales, Yuleidys, Wessjohann, Ludger A., Rivera, Daniel G.
• Format: Article
• Language: English
• Subjects: Conformation control; Cyclic peptides; Macrocyclization; Multicomponent reactions; Peptide secondary structures; Peptide stapling
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.104987

[Display omitted] •Ugi multicomponent stapling produces varied types of helical peptides.•Various Ugi reaction combinations are viable to connect the amino acid side chains.•The procedure incorporates functionalities to the staple moiety.•The helicity depends on the Ugi combination and the peptide sequence. The stabilization of helical structures by peptide stapling approaches is now a mature technology capable to provide a variety of biomedical applications. Recently, it was shown that multicomponent macrocyclization is not only an effective way to introduce conformational constraints but it also allows to incorporate additional functionalities to the staple moiety in a one-pot process. This work investigates the scope of the double Ugi multicomponent stapling approach in its capacity to produce helical peptides from unstructured sequences. For this, three different stapling combinations were implemented and the CD spectra of the cyclic peptides were measured to determine the effect of the multicomponent macrocyclization on the resulting secondary structure. A new insight into some structural factors influencing the helicity type and content is provided, along with new prospects on the utilization of this methodology to diversify the molecular tethers linking the amino acid side chains.