Dem IPB wird erneut ein beispielhaftes Handeln im Sinne einer chancengleichheitsorientierten Personal- und Organisationspolitik bescheinigt. Das Institut erhält zum 6. Mal in Folge das TOTAL E-QUALITY…
Die Plant Science Student Conference (PSSC) wird seit 20 Jahren im jährlichen Wechsel von Studierenden der beiden Leibniz-Institute IPK und IPB organisiert. Im Interview erläutern Christina Wäsch…
Ricardo, M. G.; Moya, C. G.; Pérez, C. S.; Porzel, A.; Wessjohann, L. A.; Rivera, D. G.;Improved Stability and Tunable Functionalization of Parallel β-Sheets via Multicomponent N-Alkylation of the Turn MoietyAngew. Chem. Int. Ed.59259-263(2020)DOI: 10.1002/anie.201912095
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.
Publikation
Ricardo, M. G.; Llanes, D.; Wessjohann, L. A.; Rivera, D. G.;Introducing the Petasis Reaction for Late-Stage Multicomponent Diversification, Labeling, and Stapling of PeptidesAngew. Chem. Int. Ed.582700-2704(2019)DOI: 10.1002/anie.201812620
For the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and Nϵ‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.