Omanische Heilpflanze im Fokus der Phytochemie IPB-Wissenschaftler und Partner aus Dhofar haben jüngst die omanische Heilpflanze Terminalia dhofarica unter die phytochemische Lupe genommen. Die Pflanze ist reich an…
Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Ricardo, M. G.; Vasco, A. V.; Rivera, D. G.; Wessjohann, L. A.;Stabilization of Cyclic β-Hairpins by Ugi-Reaction-Derived N-Alkylated Peptides: The Quest for Functionalized β-TurnsOrg. Lett.217307-7310(2019)DOI: 10.1021/acs.orglett.9b02592
A solid-phase approach including on-resin Ugi reactions was developed for the construction of β-hairpins. Various N-alkylated dipeptide fragments proved capable of aligning antiparallel β-sheets in a macrocyclic scaffold, thus serving as β-hairpin templates. Gramicidin S was used as the model β-hairpin to compare the Ugi-derived β-turns with the type-II′ β-turn. The results show that the multicomponent incorporation of such N-alkylated residues allows for the simultaneous stabilization and exo-cyclic functionalization of cyclic β-hairpins.
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.
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.1312726-2730(2019)DOI: 10.1002/ange.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.
Publikation
Ricardo, M. G.; Marrero, J. F.; Valdés, O.; Rivera, D. G.; Wessjohann, L. A.;A Peptide Backbone Stapling Strategy Enabled by the Multicomponent Incorporation of Amide N‐SubstituentsChem.-Eur. J.25769-774(2019)DOI: 10.1002/chem.201805318
The multicomponent backbone N‐modification of peptides on solid‐phase is presented as a powerful and general method to enable peptide stapling at the backbone instead of the side chains. This work shows that a variety of functionalized N‐substituents suitable for backbone stapling can be readily introduced by means of on‐resin Ugi multicomponent reactions conducted during solid‐phase peptide synthesis. Diverse macrocyclization chemistries were implemented with such backbone N‐substituents, including the ring‐closing metathesis, lactamization, and thiol alkylation. The backbone N‐modification method was also applied to the synthesis of α‐helical peptides by linking N‐substituents to the peptide N‐terminus, thus featuring hydrogen‐bond surrogate structures. Overall, the strategy proves useful for peptide backbone macrocyclization approaches that show promise in peptide drug discovery.