Unser 10. Leibniz Plant Biochemistry Symposium am 7. und 8. Mai war ein großer Erfolg. Thematisch ging es in diesem Jahr um neue Methoden und Forschungsansätze der Naturstoffchemie. Die exzellenten Vorträge über Wirkstoffe…
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…
Vasco, A. V.; Ceballos, L. G.; Wessjohann, L. A.; Rivera, D. G.;Multicomponent functionalization of the octreotide peptide macrocyclic scaffoldEur. J. Org. Chem.2022e202200687(2022)DOI: 10.1002/ejoc.202200687
The replacement of the disulfide bridge by other types of side chain linkages has been a continuous endeavor in the development of cyclic peptide drugs with improved metabolic stability. Octreotide is a potent and selective somatostatin analog that has been used as an anticancer agent, in radiolabeled conjugates for the localization of tumors and as targeting moiety in peptide-drug conjugates. Here, we describe an onresin methodology based on a multicomponent macrocyclization that enables the substitution of the disulfide bond by a tertiary lactam bridge functionalized with a variety of exocyclic moieties, including lipids, fluorophores, and charged groups. Conformational analysis in comparison with octreotide provides key information on the type of functionalization permitting the conformational mimicry of the bioactive peptide.
Publikation
Ditfe, T.; Bette, E.; N. Sultani, H.; Otto, A.; Wessjohann, L. A.; Arnold, N.; Westermann, B.;Synthesis and biological evaluation of highly potent fungicidal deoxy‐hygrophoronesEur. J. Org. Chem.20213827-3836(2021)DOI: 10.1002/ejoc.202100729
Although stripped from hydroxyl-groups, deoxygenated
hygrophorones remain highly active against severe phytopathogens. The
synthesis to these natural product congeners is achieved in
rearrangement sequences, with an optimized deprotection strategy
avoiding retro-aldol reactions. The activities are comparable to
fungicides used in agriculture.
Based on naturally occurring hygrophorones, racemic di-
and mono-hydroxylated cyclopentenones bearing an aliphatic side chain
have been produced in short synthetic sequences starting from furfuryl
aldehyde. For the series of dihydroxylated trans-configured derivatives, an Achmatowicz-rearrangement and a Caddick-ring contraction were employed, and for the series of trans-configured
mono-hydroxylated derivatives a Piancatelli-rearrangement. All final
products showed good to excellent fungicidal activities against the
plant pathogens B. cinerea, S. tritici and P. infestans.
Publikation
Mora Huertas, A. C.; Schmelzer, C. E.; Luise, C.; Sippl, W.; Pietzsch, M.; Hoehenwarter, W.; Heinz, A.;Degradation of tropoelastin and skin elastin by neprilysinBiochimie14673-78(2018)DOI: 10.1016/j.biochi.2017.11.018
Neprilysin is also known as skin fibroblast-derived elastase, and its up-regulation during aging is associated with impairments of the elastic fiber network, loss of skin elasticity and wrinkle formation. However, information on its elastase activity is still limited. The aim of this study was to investigate the degradation of fibrillar skin elastin by neprilysin and the influence of the donor's age on the degradation process using mass spectrometry and bioinformatics approaches. The results showed that cleavage by neprilysin is dependent on previous damage of elastin. While neprilysin does not cleave young and intact skin elastin well, it degrades elastin fibers from older donors, which may further promote aging processes. With regards to the cleavage behavior of neprilysin, a strong preference for Gly at P1 was found, while Gly, Ala and Val were well accepted at P1′ upon cleavage of tropoelastin and skin elastin. The results of the study indicate that the progressive release of bioactive elastin peptides by neprilysin upon skin aging may enhance local tissue damage and accelerate extracellular matrix aging processes.
Publikation
Aleksis, R.; Oleskovs, F.; Jaudzems, K.; Pahnke, J.; Biverstål, H.;Structural studies of amyloid-β peptides: Unlocking the mechanism of aggregation and the associated toxicityBiochimie140176-192(2017)DOI: 10.1016/j.biochi.2017.07.011
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases worldwide. Formation of amyloid plaques consisting of amyloid-β peptides (Aβ) is one of the hallmarks of AD. Several lines of evidence have shown a correlation between the Aβ aggregation and the disease development. Extensive research has been conducted with the aim to reveal the structures of the neurotoxic Aβ aggregates. However, the exact structure of pathological aggregates and mechanism of the disease still remains elusive due to complexity of the occurring processes and instability of various disease-relevant Aβ species. In this article we review up-to-date structural knowledge about amyloid-β peptides, focusing on data acquired using solution and solid state NMR techniques. Furthermore, we discuss implications from these structural studies on the mechanisms of aggregation and neurotoxicity.