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Molecular Signal Processing
Bioorganic Chemistry
Biochemistry of Plant Interactions
Cell and Metabolic Biology
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Publications
Publications - Cell and Metabolic Biology
Publications
A bottleneck in the development of new anti‐cancer drugs is the recognition of their mode of action (MoA). Metabolomics combined with machine learning allowed to predict MoAs of novel anti‐proliferative drug candidates, focusing on human prostate cancer cells (PC‐3). As proof of concept, 38 drugs are studied with known effects on 16 key processes of cancer metabolism, profiling low molecular weight intermediates of the central carbon and cellular energy metabolism (CCEM) by LC‐MS/MS. These metabolic patterns unveiled distinct MoAs, enabling accurate MoA predictions for novel agents by machine learning. The transferability of MoA predictions based on PC‐3 cell treatments is validated with two other cancer cell models, i.e., breast cancer and Ewing\'s sarcoma, and show that correct MoA predictions for alternative cancer cells are possible, but still at some expense of prediction quality. Furthermore, metabolic profiles of treated cells yield insights into intracellular processes, exemplified for drugs inducing different types of mitochondrial dysfunction. Specifically, it is predicted that pentacyclic triterpenes inhibit oxidative phosphorylation and affect phospholipid biosynthesis, as confirmed by respiration parameters, lipidomics, and molecular docking. Using biochemical insights from individual drug treatments, this approach offers new opportunities, including the optimization of combinatorial drug applications.
Publications
In barley leaves a group of genes is expressed in response to treatment with jasmonates and abscisic acid (ABA) [21]. One of these genes coding for a jasmonate-induced protein of 23 kDa (JIP-23) was analyzed to find out the link between ABA and jasmonates by recording its expression upon modulating independently, the endogenous level of both of them. By use of inhibitors of JA synthesis and ABA degradation, and the ABA-deficient mutant Az34, as well as of cultivar-specific differences, it was shown that endogenous jasmonate increases are necessary and sufficient for expression of this gene. The endogenous rise of ABA did not induce synthesis of JIP-23, whereas exogenous ABA did not act via jasmonates. Different signalling pathways are suggested and discussed.
Publications
This article surveys the currently isolated and identified GA conjugates, their synthesis and evaluates modern methods for analysing GA glucose conjugates. The metabolism of applied GAs in higher plant systems leading, in most cases, to GA conjugates is also considered. The enzymology of the formation and hydrolysis of GA glucose conjugates is discussed in connection with their possible physiological function.
Publications
Data on the occurrence of free and conjugated gibberellins in different tribes of Gramineae are compiled and discussed with regard to their biosynthetic pathways. From the gibberellins detected so far the functioning of both the early 13-hydroxylation and the non-3,13-hydroxylation pathway of GA biosynthesis in gramineous plants can be deduced and the discovery of further gibberellin conjugates may be expected.
This page was last modified on 27 Jan 2025 .
