TY - CONF A1 - Kuner, Maximilian A1 - Kühn, Susanne A1 - Koch, Matthias A1 - Haase, Hajo T1 - Cleaving ergot alkaloids - development of a novel food screening method N2 - Mycotoxins (toxic compounds formed by fungi) in food and feed have caused problems for mankind since the beginning of time. The group of ergot alkaloids plays a special role in human history. Several tens of thousands of deaths during the middle ages caused by to ergotism (the disease caused by continuous intake of ergot alkaloid contaminated food) underscore the importance of reliable analytical methods to ensure food safety. More than 50 compounds belong to the group of ergot alkaloids. The 12 most found structures – the major ergot alkaloids – are typically measured, when it comes to ergot alkaloid quantification. High performance liquid chromatography (HPLC) with a fluorescence detector (FLD) is typically used to quantify the ergot alkaloid content. The main disadvantage of this method are the high costs for calibration standards (12 different calibration substances are required). But also, the time and effort required for the analysis of 12 peaks and overlapping signals that occur in complex food samples such as bread. As all ergot alkaloids share the ergoline structure and just differ in the substituents attached to this backbone, measurement of all ergot alkaloids in one sum parameter presents a time and cost saving alternative. The most important step for the development of such a sum parameter method is the reaction used to transfer all ergot alkaloids to one uniform structure. Two promising reactions, the acidic esterification to lysergic acid methyl ester and hydrazinolysis to lysergic acid hydrazide, were examined for possible use in a routine analysis method. In addition to yield and reaction rate, factors such as handling of the reaction and the possibility of parallel sample workup play a role. T2 - Adlershofer Forschungsforum 2022 CY - Berlin, Germany DA - 11.11.2022 KW - Ergot alkaloids KW - Screening PY - 2022 AN - OPUS4-56585 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kader, A. A1 - Brangsch, J. A1 - Kaufmann, Jan Ole A1 - Zhao, J. A1 - Mangarova, D. B. A1 - Moeckel, J. A1 - Adams, L. C. A1 - Sack, I. A1 - Taupitz, M. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Molecular MR Imaging of Prostate Cancer JF - Biomedicines N2 - This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size. KW - Prostate cancer KW - Magnetic resonance imaging KW - Molecular imaging KW - Imaging KW - Molecular marker KW - Screening KW - MRI KW - Diagnosis PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-519503 DO - https://doi.org/10.3390/biomedicines9010001 VL - 9 IS - 1 SP - 1 EP - 17 PB - MDPI CY - Basel AN - OPUS4-51950 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Remmler, Dario A1 - Schwaar, Timm A1 - Weller, Michael G. A1 - Börner, H. G. T1 - Two-dimensional screening of large peptide libraries to identify solubilizers with tailored release capabilities N2 - Small organic molecule drugs are one of the key classes, taking increasingly important roles in modern drug development strategies. With the focus on small molecule drugs, difficulties originate frequently from a pronounced lipophilic character, resulting in poor water solubility, low bioavailability and unfavored pharmacokinetics. Recently, peptide-poly(ethylene glycol) conjugates (peptide-PEG conjugates) were described as precisely tunable platforms to solubilize a broad scope of fluorescent or non-fluorescent small organic molecules [1-2]. Selection of drug hosting peptides was achieved by combinatorial means, which can further be extended by implementation of a drug release screening step. One-bead-one-compound peptide libraries are powerful tools to select high affinity binders. However, the selection of positive hits from the peptide libraries remains tedious as it occurs by handpicking, strongly limiting the pool of investigated beads. Here we report our recent results on improving the analytical platform, using automated fluorescence scanning and MALDI-ToF-ToF MS/MS imaging to screen larger sets of beads, broadening the statistical base and unraveling more precisely suitable peptides. The screening puts special emphasis on loading capacities and drug-release of transporters by performing additional washing steps in different media (cf. Fig. 1). Peptides representing strong, medium, weak releaser were chosen for further analysis and synthesized as peptide-polymer transporters. Release was analyzed by fluorescence anisotropy and fluorescence correlation spectroscopy, due to the fluorescent characteristics of the drug. Solubilization studies confirmed sufficient loading capacities for a potential anti-Alzheimer disease drug of three transporter molecules representing strong/weak drug releaser, reaching solubilization of up to 1:3.4 (µmol drug/µmol conjugate). Fluorescence anisotropy and fluorescence correlation spectroscopy of the drug-loaded transporter showed significant differences in drug releasing properties, confirming the screening process. T2 - 15th European Symposium on Controlled Drug Delivery CY - Egmond aan Zee, The Netherlands DA - 11.04.2018 KW - Combinatorial library KW - Bioconjugates KW - Screening KW - Pharmaceuticals KW - Biotechnology KW - Drugs PY - 2018 AN - OPUS4-44713 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Schwaar, Timm A1 - Lettow, Maike A1 - Remmler, Dario A1 - Börner, H. G. A1 - Weller, Michael G. T1 - Efficient Screening of Combinatorial Peptide Libraries by Spatially Ordered Beads Immobilized on Conventional Glass Slides JF - High-Throughput N2 - Screening of one-bead-one-compound (OBOC) libraries is a proven procedure for the identification of protein-binding ligands. The demand for binders with high affinity and specificity towards various targets has surged in the biomedical and pharmaceutical field in recent years. The traditional peptide screening involves tedious steps such as affinity selection, bead picking, sequencing, and characterization. Herein, we present a high-throughput “all-on-one chip” system to avoid slow and technically complex bead picking steps. On a traditional glass slide provided with an electrically conductive tape, beads of a combinatorial peptide library are aligned and immobilized by application of a precision sieve. Subsequently, the chip is incubated with a fluorophore-labeled target protein. In a fluorescence scan followed by matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF) mass spectrometry, high-affinity binders are directly and unambiguously sequenced with high accuracy without picking of the positive beads. The use of an optimized ladder sequencing approach improved the accuracy of the de-novo sequencing step to nearly 100%. The new technique was validated by employing a FLAG-based model system, identifying new peptide binders for the monoclonal M2 anti-FLAG antibody, and was finally utilized to search for IgG-binding peptides. In the present format, more than 30,000 beads can be screened on one slide. KW - Peptide library KW - HTS KW - Target KW - MALDI KW - Mass spectrometry KW - Biochip KW - Lab-on-a-Chip KW - Array KW - Screening KW - Ladder sequencing KW - Binder KW - Pharmaceutical PY - 2019 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-478973 UR - https://www.mdpi.com/2571-5135/8/2/11 DO - https://doi.org/10.3390/ht8020011 VL - 8 IS - 2 SP - 1 EP - 15 PB - MDPI CY - Basel AN - OPUS4-47897 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -