A biological evaluation of a library of extracts from entomopathogen strains showed that sp. extract has significant antimicrobial and insecticidal activities. Three hydroxyacyl-phenylalanine derivatives were isolated from this strain. Their structures were elucidated by a comprehensive analysis of their NMR and MS spectroscopic data. The antimicrobial and insecticidal potencies of these compounds were evaluated, and compound showed 67% mortality against larvae at a concentration of 100 ppm, and a minimum inhibitory concentration (MIC) of 16 µg/mL against methicillin-resistant . Subsequently, hydroxyacyl-phenylalanine analogues were synthesized to better understand the structure-activity relationships within this class of compounds. Bioassays highlighted the antimicrobial potential of analogues containing saturated medium-chain fatty acids (12 or 14 carbons), whereas an unsaturated long-chain fatty acid (16 carbons) imparted larvicidal activity. Finally, using a molecular networking-based approach, several close analogues of the isolated and newly synthesized lipoamino acids were discovered in the sp. extract.
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http://dx.doi.org/10.3390/ijms20051083 | DOI Listing |
Eur J Pharm Sci
February 2025
Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität Munich, Butenandtstrasse 5-13, 81377 Munich, Germany; Center for Nanoscience (CeNS), LMU Munich, 80799 Munich, Germany; CNATM - Cluster for Nucleic Acid Therapeutics Munich, Germany. Electronic address:
Nanoscale
July 2024
Pharmaceutical Biotechnology, Department of Pharmacy, LMU Munich, Butenandtstr. 5-13, 81377 Munich, Germany.
Double pH-responsive xenopeptides comprising polar ionizable succinoyl tetraethylene pentamine (Stp) motifs and lipophilic ionizable lipoamino fatty acids (LAFs) were recently found to efficiently transfect mRNA and pDNA at low doses. However, potency was often accompanied with cytotoxicity at higher doses. Insertion of bioreducible disulfide building blocks (ssbb) or non-reducible hydrophobic spacers between polar and apolar ionizable domains of LAF-Stp carriers should mitigate toxicity of xenopeptides.
View Article and Find Full Text PDFSmall
October 2024
Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität (LMU), 81377, Munich, Germany.
Although small-interfering RNAs (siRNAs) are specific silencers for numerous disease-related genes, their clinical applications still require safe and effective means of delivery into target cells. Highly efficient lipid nanoparticles (LNPs) are developed for siRNA delivery, showcasing the advantages of novel pH-responsive lipoamino xenopeptide (XP) carriers. These sequence-defined XPs are assembled by branched lysine linkages between cationizable polar succinoyl tetraethylene pentamine (Stp) units and apolar lipoamino fatty acids (LAFs) at various ratios into bundle or U-shape topologies.
View Article and Find Full Text PDFJ Am Soc Mass Spectrom
May 2024
Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé, MetaboHUB, 91191 Gif-sur-Yvette, France.
In untargeted metabolomics, the unambiguous identification of metabolites remains a major challenge. This requires high-quality spectral libraries for reliable metabolite identification, which is essential for translating metabolomics data into meaningful biological information. Several attempts have been made to generate reproducible product ion spectra (PIS) under a low collision energy () regime and nonresonant collisional conditions but have not fully succeeded.
View Article and Find Full Text PDFEur J Pharm Biopharm
January 2024
Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität Munich, Butenandtstrasse 5-13, 81377 Munich, Germany; Center for Nanoscience, Ludwig-Maximilians-Universität Munich, Geschwister-Scholl-Platz 1, 80539 Munich, Germany; CNATM - Cluster for Nucleic Acid Therapeutics Munich, Germany. Electronic address:
Messenger RNA (mRNA) is a powerful tool for nucleic acid-based therapies and vaccination, but efficient and specific delivery to target tissues remains a significant challenge. In this study, we demonstrate lipoamino xenopeptide carriers as components of highly efficient mRNA LNPs. These lipo-xenopeptides are defined as 2D sequences in different 3D topologies (bundles or different U-shapes).
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