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.
Palm-Forster, M. A. T.; Eschen-Lippold, L.; Uhrig, J.; Scheel, D.; Lee, J.;A novel family of proline/serine-rich proteins, which are phospho-targets of stress-related mitogen-activated protein kinases, differentially regulates growth and pathogen defense in Arabidopsis thalianaPlant Mol. Biol.95123-140(2017)DOI: 10.1007/s11103-017-0641-5
The molecular actions of mitogen-activated protein kinases (MAPKs) are ultimately accomplished by the substrate proteins where phosphorylation affects their molecular properties and function(s), but knowledge regarding plant MAPK substrates is currently still fragmentary. Here, we uncovered a previously uncharacterized protein family consisting of three proline/serine-rich proteins (PRPs) that are substrates of stress-related MAPKs. We demonstrated the importance of a MAPK docking domain necessary for protein–protein interaction with MAPKs and consequently also for phosphorylation. The main phosphorylated site was mapped to a residue conserved between all three proteins, which when mutated to a non-phosphorylatable form, differentially affected their protein stability. Together with their distinct gene expression patterns, this differential accumulation of the three proteins upon phosphorylation probably contributes to their distinct function(s). Transgenic over-expression of PRP, the founding member, led to plants with enhanced resistance to Pseudomonas syringae pv. tomato DC3000. Older plants of the over-expressing lines have curly leaves and were generally smaller in stature. This growth phenotype was lost in plants expressing the phosphosite variant, suggesting a phosphorylation-dependent effect. Thus, this novel family of PRPs may be involved in MAPK regulation of plant development and / or pathogen resistance responses. As datamining associates PRP expression profiles with hypoxia or oxidative stress and PRP-overexpressing plants have elevated levels of reactive oxygen species, PRP may connect MAPK and oxidative stress signaling.