Improved Stability and Tunable Functionalization of Parallel β‐Sheets via Multicomponent N‐Alkylation of the Turn Moiety

In contrast to the myriad of methods available to produce α‐helices and antiparallel β‐sheets in synthetic peptides, just a few are known for the construction of stable, non‐cyclic parallel β‐sheets. Herein, we report an efficient on‐resin approach for the assembly of parallel β‐sheet peptides in wh...

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Bibliographic Details
Published in:Angewandte Chemie 2020-01, Vol.132 (1), p.265-269
Main Authors: Ricardo, Manuel G., Moya, Celia G., Pérez, Carlos S., Porzel, Andrea, Wessjohann, Ludger A., Rivera, Daniel G.
Format: Article
Language:English
Subjects:
Alkylation
Chemistry
Circular dichroism
Conjugation
Construction
Dichroism
Festphasensynthese
Helices
Materials handling
Mehrkomponenten-Reaktionen
NMR
Nuclear magnetic resonance
Peptide
Peptides
Production methods
Resins
Sekundärstrukturen
Sheets
Stability
Synthetic peptides
β-Faltblätter
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Summary:In contrast to the myriad of methods available to produce α‐helices and antiparallel β‐sheets in synthetic peptides, just a few are known for the construction of stable, non‐cyclic parallel β‐sheets. Herein, we report an efficient on‐resin approach for the assembly of parallel β‐sheet peptides in which the N‐alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N‐alkylated turn using the Ugi reaction on varied isocyano‐resins. This four‐component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better‐structured and more stable parallel β‐sheets in the N‐alkylated peptides compared to the non‐functionalized variants. Eine N‐Alkylierung auf Basis der Ugi‐Reaktion an geeigneter Position in der Schleifeneinheit eines nichtcyclischen parallelen Peptid‐β‐Faltblatts erhöht die Faltungsneigung und thermische Stabilität in wässriger Lösung. Sie ermöglicht auch die Einführung verschiedener funktioneller Gruppen, z. B. einer zusätzlichen kationischen Gruppe zur Vermeidung von Aggregation oder eines Thiols zur Konjugation mit einem Fluoreszenzmarker.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201912095