@article{BurgerRumpfDoetal.2021, author = {Burger, Ren{\´e} and Rumpf, Jessica and Do, Xuan Tung and Monakhova, Yulia and Diehl, Bernd W. K. and Rehahn, Matthias and Schulze, Margit}, title = {Is NMR combined with multivariate regression applicable for the molecular weight determination of randomly cross-linked polymers such as lignin?}, series = {ACS Omega}, volume = {6}, journal = {ACS Omega}, number = {44}, publisher = {ACS Publications}, address = {Washington, DC}, issn = {2470-1343}, doi = {10.1021/acsomega.1c03574}, pages = {29516 -- 29524}, year = {2021}, abstract = {The molecular weight properties of lignins are one of the key elements that need to be analyzed for a successful industrial application of these promising biopolymers. In this study, the use of 1H NMR as well as diffusion-ordered spectroscopy (DOSY NMR), combined with multivariate regression methods, was investigated for the determination of the molecular weight (Mw and Mn) and the polydispersity of organosolv lignins (n = 53, Miscanthus x giganteus, Paulownia tomentosa, and Silphium perfoliatum). The suitability of the models was demonstrated by cross validation (CV) as well as by an independent validation set of samples from different biomass origins (beech wood and wheat straw). CV errors of ca. 7-9 and 14-16\% were achieved for all parameters with the models from the 1H NMR spectra and the DOSY NMR data, respectively. The prediction errors for the validation samples were in a similar range for the partial least squares model from the 1H NMR data and for a multiple linear regression using the DOSY NMR data. The results indicate the usefulness of NMR measurements combined with multivariate regression methods as a potential alternative to more time-consuming methods such as gel permeation chromatography.}, language = {en} } @article{MonakhovaDiehl2022, author = {Monakhova, Yulia and Diehl, Bernd W.K.}, title = {Nuclear magnetic resonance spectroscopy as an elegant tool for a complete quality control of crude heparin material}, series = {Journal of Pharmaceutical and Biomedical Analysis}, volume = {219}, journal = {Journal of Pharmaceutical and Biomedical Analysis}, number = {Article number: 114915}, publisher = {Elsevier}, address = {New York, NY}, issn = {0731-7085}, doi = {10.1016/j.jpba.2022.114915}, year = {2022}, abstract = {Nuclear magnetic resonance (NMR) spectrometric methods for the quantitative analysis of pure heparin in crude heparin is proposed. For quantification, a two-step routine was developed using a USP heparin reference sample for calibration and benzoic acid as an internal standard. The method was successfully validated for its accuracy, reproducibility, and precision. The methodology was used to analyze 20 authentic porcine heparinoid samples having heparin content between 4.25 w/w \% and 64.4 w/w \%. The characterization of crude heparin products was further extended to a simultaneous analysis of these common ions: sodium, calcium, acetate and chloride. A significant, linear dependence was found between anticoagulant activity and assayed heparin content for thirteen heparinoids samples, for which reference data were available. A Diffused-ordered NMR experiment (DOSY) can be used for qualitative analysis of specific glycosaminoglycans (GAGs) in heparinoid matrices and, potentially, for quantitative prediction of molecular weight of GAGs. NMR spectrometry therefore represents a unique analytical method suitable for the simultaneous quantitative control of organic and inorganic composition of crude heparin samples (especially heparin content) as well as an estimation of other physical and quality parameters (molecular weight, animal origin and activity).}, language = {en} } @article{MonakhovaDiehl2021, author = {Monakhova, Yulia and Diehl, Bernd W. K.}, title = {Simplification of NMR Workflows by Standardization Using 2H Integral of Deuterated Solvent as Applied to Aloe vera Preparations}, series = {Applied Magnetic Resonance}, volume = {52}, journal = {Applied Magnetic Resonance}, number = {11}, publisher = {Springer}, address = {Cham}, issn = {1613-7507}, doi = {10.1007/s00723-021-01393-4}, pages = {1591 -- 1600}, year = {2021}, abstract = {In this study, a recently proposed NMR standardization approach by 2H integral of deuterated solvent for quantitative multicomponent analysis of complex mixtures is presented. As a proof of principle, the existing NMR routine for the analysis of Aloe vera products was modified. Instead of using absolute integrals of targeted compounds and internal standard (nicotinamide) from 1H-NMR spectra, quantification was performed based on the ratio of a particular 1H-NMR compound integral and 2H-NMR signal of deuterated solvent D2O. Validation characteristics (linearity, repeatability, accuracy) were evaluated and the results showed that the method has the same precision as internal standardization in case of multicomponent screening. Moreover, a dehydration process by freeze drying is not necessary for the new routine. Now, our NMR profiling of A. vera products needs only limited sample preparation and data processing. The new standardization methodology provides an appealing alternative for multicomponent NMR screening. In general, this novel approach, using standardization by 2H integral, benefits from reduced sample preparation steps and uncertainties, and is recommended in different application areas (purity determination, forensics, pharmaceutical analysis, etc.).}, language = {en} } @article{AdelsMonakhova2024, author = {Adels, Klaudia and Monakhova, Yulia}, title = {Low-field NMR spectroscopic study of e-cigarettes: Is determination of only nicotine and organic carrier solvents possible?}, series = {Microchemical Journal}, volume = {203}, journal = {Microchemical Journal}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1095-9149}, doi = {10.1016/j.microc.2024.110859}, pages = {9 Seiten}, year = {2024}, abstract = {Electronic cigarettes (e-cigarettes) have become popular worldwide with the market growing exponentially in some countries. The absence of product standards and safety regulations requires urgent development of analytical methodologies for the holistic control of the growing diversity of such products. An approach based on low-field nuclear magnetic resonance (LF-NMR) at 80 MHz is presented for the simultaneous determination of key parameters: carrier solvents (vegetable glycerine (VG), propylene glycol (PG) and water), total nicotine as well as free-base nicotine fraction. Moreover, qualitative and quantitative determination of fourteen weak organic acids deliberately added to enhance sensory characteristics of e-cigarettes was possible. In most cases these parameters can be rapidly and conveniently determined without using any sample manipulation such as dilution, extraction or derivatization steps. The method was applied for 37 authentic e-cigarettes samples. In particular, eight different organic acids with the content up to 56 mg/mL were detected. Due to its simplicity, the method can be used in routine regulatory control as well as to study release behaviour of nicotine and other e-cigarettes constituents in different products.}, language = {en} } @article{BurgerLindnerRumpfetal.2022, author = {Burger, Ren{\´e} and Lindner, Simon and Rumpf, Jessica and Do, Xuan Tung and Diehl, Bernd W.K. and Rehahn, Matthias and Monakhova, Yulia and Schulze, Margit}, title = {Benchtop versus high field NMR: Comparable performance found for the molecular weight determination of lignin}, series = {Journal of Pharmaceutical and Biomedical Analysis}, volume = {212}, journal = {Journal of Pharmaceutical and Biomedical Analysis}, number = {Article number: 114649}, publisher = {Elsevier}, address = {New York, NY}, isbn = {0731-7085}, doi = {10.1016/j.jpba.2022.114649}, year = {2022}, abstract = {Lignin is a promising renewable biopolymer being investigated worldwide as an environmentally benign substitute of fossil-based aromatic compounds, e.g. for the use as an excipient with antioxidant and antimicrobial properties in drug delivery or even as active compound. For its successful implementation into process streams, a quick, easy, and reliable method is needed for its molecular weight determination. Here we present a method using 1H spectra of benchtop as well as conventional NMR systems in combination with multivariate data analysis, to determine lignin's molecular weight (Mw and Mn) and polydispersity index (PDI). A set of 36 organosolv lignin samples (from Miscanthus x giganteus, Paulownia tomentosa and Silphium perfoliatum) was used for the calibration and cross validation, and 17 samples were used as external validation set. Validation errors between 5.6\% and 12.9\% were achieved for all parameters on all NMR devices (43, 60, 500 and 600 MHz). Surprisingly, no significant difference in the performance of the benchtop and high-field devices was found. This facilitates the application of this method for determining lignin's molecular weight in an industrial environment because of the low maintenance expenditure, small footprint, ruggedness, and low cost of permanent magnet benchtop NMR systems.}, language = {en} } @article{MonakhovaSobolevaFedotovaetal.2022, author = {Monakhova, Yulia and Soboleva, Polina M. and Fedotova, Elena S. and Musina, Kristina T. and Burmistrova, Natalia A.}, title = {Quantum chemical calculations of IR spectra of heparin disaccharide subunits}, series = {Computational and Theoretical Chemistry}, volume = {1217}, journal = {Computational and Theoretical Chemistry}, number = {Article number: 113891}, publisher = {Elsevier}, address = {New York, NY}, isbn = {2210-271X}, doi = {10.1016/j.comptc.2022.113891}, year = {2022}, abstract = {Heparin is a natural polysaccharide, which plays essential role in many biological processes. Alterations in building blocks can modify biological roles of commercial heparin products, due to significant changes in the conformation of the polymer chain. The variability structure of heparin leads to difficulty in quality control using different analytical methods, including infrared (IR) spectroscopy. In this paper molecular modelling of heparin disaccharide subunits was performed using quantum chemistry. The structural and spectral parameters of these disaccharides have been calculated using RHF/6-311G. In addition, over-sulphated chondroitin sulphate disaccharide was studied as one of the most widespread contaminants of heparin. Calculated IR spectra were analyzed with respect to specific structure parameters. IR spectroscopic fingerprint was found to be sensitive to substitution pattern of disaccharide subunits. Vibrational assignments of calculated spectra were correlated with experimental IR spectral bands of native heparin. Chemometrics was used to perform multivariate analysis of simulated spectral data.}, language = {en} } @article{BurmistrovaSobolevaMonakhova2021, author = {Burmistrova, Natalia A. and Soboleva, Polina M. and Monakhova, Yulia}, title = {Is infrared spectroscopy combined with multivariate analysis a promising tool for heparin authentication?}, series = {Journal of Pharmaceutical and Biomedical Analysis}, volume = {194}, journal = {Journal of Pharmaceutical and Biomedical Analysis}, number = {Article number: 113811}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {0731-7085}, doi = {10.1016/j.jpba.2020.113811}, year = {2021}, abstract = {The investigation of the possibility to determine various characteristics of powder heparin (n = 115) was carried out with infrared spectroscopy. The evaluation of heparin samples included several parameters such as purity grade, distributing company, animal source as well as heparin species (i.e. Na-heparin, Ca-heparin, and heparinoids). Multivariate analysis using principal component analysis (PCA), soft independent modelling of class analogy (SIMCA), and partial least squares - discriminant analysis (PLS-DA) were applied for the modelling of spectral data. Different pre-processing methods were applied to IR spectral data; multiplicative scatter correction (MSC) was chosen as the most relevant. Obtained results were confirmed by nuclear magnetic resonance (NMR) spectroscopy. Good predictive ability of this approach demonstrates the potential of IR spectroscopy and chemometrics for screening of heparin quality. This approach, however, is designed as a screening tool and is not considered as a replacement for either of the methods required by USP and FDA.}, language = {en} } @article{HaegerBongaertsSiegert2022, author = {Haeger, Gerrit and Bongaerts, Johannes and Siegert, Petra}, title = {A convenient ninhydrin assay in 96-well format for amino acid-releasing enzymes using an air-stable reagent}, series = {Analytical Biochemistry}, journal = {Analytical Biochemistry}, number = {624}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1096-0309}, doi = {10.1016/j.ab.2022.114819}, pages = {Artikel 114819}, year = {2022}, abstract = {An improved and convenient ninhydrin assay for aminoacylase activity measurements was developed using the commercial EZ Nin™ reagent. Alternative reagents from literature were also evaluated and compared. The addition of DMSO to the reagent enhanced the solubility of Ruhemann's purple (RP). Furthermore, we found that the use of a basic, aqueous buffer enhances stability of RP. An acidic protocol for the quantification of lysine was developed by addition of glacial acetic acid. The assay allows for parallel processing in a 96-well format with measurements microtiter plates.}, language = {en} } @article{WeldenJablonskiWegeetal.2021, author = {Welden, Rene and Jablonski, Melanie and Wege, Christina and Keusgen, Michael and Wagner, Patrick Hermann and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Light-Addressable Actuator-Sensor Platform for Monitoring and Manipulation of pH Gradients in Microfluidics: A Case Study with the Enzyme Penicillinase}, series = {Biosensors}, volume = {11}, journal = {Biosensors}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2079-6374}, doi = {10.3390/bios11060171}, pages = {Artikel 171}, year = {2021}, abstract = {The feasibility of light-addressed detection and manipulation of pH gradients inside an electrochemical microfluidic cell was studied. Local pH changes, induced by a light-addressable electrode (LAE), were detected using a light-addressable potentiometric sensor (LAPS) with different measurement modes representing an actuator-sensor system. Biosensor functionality was examined depending on locally induced pH gradients with the help of the model enzyme penicillinase, which had been immobilized in the microfluidic channel. The surface morphology of the LAE and enzyme-functionalized LAPS was studied by scanning electron microscopy. Furthermore, the penicillin sensitivity of the LAPS inside the microfluidic channel was determined with regard to the analyte's pH influence on the enzymatic reaction rate. In a final experiment, the LAE-controlled pH inhibition of the enzyme activity was monitored by the LAPS.}, language = {en} } @article{NiedermeierPennerUsherovichetal.2023, author = {Niedermeier, Jana and Penner, Crystal and Usherovich, Samuel and B{\´e}langer-Champagne, Camille and Paulßen, Elisabeth and Hoehr, Cornelia}, title = {Optical Fibers as Dosimeter Detectors for Mixed Proton/Neutron Fields - A Biological Dosimeter}, series = {electronics}, volume = {12}, journal = {electronics}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2079-9292}, doi = {10.3390/electronics12020324}, pages = {11 Seiten}, year = {2023}, abstract = {In recent years, proton therapy has gained importance as a cancer treatment modality due to its conformality with the tumor and the sparing of healthy tissue. However, in the interaction of the protons with the beam line elements and patient tissues, potentially harmful secondary neutrons are always generated. To ensure that this neutron dose is as low as possible, treatment plans could be created to also account for and minimize the neutron dose. To monitor such a treatment plan, a compact, easy to use, and inexpensive dosimeter must be developed that not only measures the physical dose, but which can also distinguish between proton and neutron contributions. To that end, plastic optical fibers with scintillation materials (Gd₂O₂S:Tb, Gd₂O₂S:Eu, and YVO₄:Eu) were irradiated with protons and neutrons. It was confirmed that sensors with different scintillation materials have different sensitivities to protons and neutrons. A combination of these three scintillators can be used to build a detector array to create a biological dosimeter.}, language = {en} } @article{LuisierLempiaeinenScherbichleretal.2014, author = {Luisier, Rapha{\"e}lle and Lempi{\"a}inen, Harri and Scherbichler, Nina and Braeuning, Albert and Geissler, Miriam and Dubost, Valerie and M{\"u}ller, Arne and Scheer, Nico and Chibout, Salah-Dine and Hara, Hisanori and Picard, Frank and Theil, Diethilde and Couttet, Philippe and Vitobello, Antonio and Grenet, Olivier and Grasl-Kraupp, Bettina and Ellinger-Ziegelbauer, Heidrung and Thomson, John P. and Meehan, Richard R. and Elcombe, Clifford R. and Henderson, Colin J. and Wolf, C. Roland and Schwarz, Michael and Moulin, Pierre and Terranova, Remi and Moggs, Jonathan G.}, title = {Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors}, series = {Toxicological Sciences}, volume = {139}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {https://doi.org/10.1093/toxsci/kfu038}, pages = {501 -- 511}, year = {2014}, abstract = {The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.}, language = {en} } @article{ScheerMclaughlinRodeetal.2014, author = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.}, title = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057885}, pages = {1022 -- 1030}, year = {2014}, abstract = {In humans, 75\% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80\% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15\%) and larger livers (20\%). Changes in hepatic morphology and a decreased blood glucose (30\%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.}, language = {en} } @article{ScheerHendersonKapelyukhetal.2019, author = {Scheer, Nico and Henderson, Colin James and Kapelyukh, Yury and Rode, Anja and Mclaren, Aileen W. and MacLeod, Alastair Kenneth and Lin, De and Wright, Jayne and Stanley, Lesley and Wolf, C. Roland}, title = {An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials}, series = {Drug Metabolism and Disposition}, journal = {Drug Metabolism and Disposition}, number = {Early view}, doi = {10.1124/dmd.119.086397}, pages = {69 Seiten}, year = {2019}, language = {en} } @article{WilsonWilsonScheeretal.2017, author = {Wilson, Ian D. and Wilson, Claire E. and Scheer, Nico and Dickie, A.P. and Schreiter, K. and Wilson, E. M. and Riley, R. J. and Wehr, R. and Bial, J.}, title = {The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice}, series = {Biochemical pharmacology}, volume = {Volume 135}, journal = {Biochemical pharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2968}, doi = {10.1016/j.bcp.2017.03.015}, pages = {139 -- 150}, year = {2017}, language = {en} } @article{HoughNalwalkDingetal.2015, author = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico}, title = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {9}, issn = {1521-009x}, doi = {10.1124/dmd.115.065490}, pages = {1326 -- 1330}, year = {2015}, language = {en} } @article{HaegerProbstJaegeretal.2023, author = {Haeger, Gerrit and Probst, Johanna and Jaeger, Karl-Erich and Bongaerts, Johannes and Siegert, Petra}, title = {Novel aminoacylases from Streptomyces griseus DSM 40236 and their recombinant production in Streptomyces lividans}, series = {FEBS Open Bio}, volume = {13}, journal = {FEBS Open Bio}, number = {12}, publisher = {Wiley}, address = {Hoboken, NJ}, issn = {2211-5463}, doi = {10.1002/2211-5463.13723}, pages = {2224 -- 2238}, year = {2023}, abstract = {Amino acid-based surfactants are valuable compounds for cosmetic formulations. The chemical synthesis of acyl-amino acids is conventionally performed by the Schotten-Baumann reaction using fatty acyl chlorides, but aminoacylases have also been investigated for use in biocatalytic synthesis with free fatty acids. Aminoacylases and their properties are diverse; they belong to different peptidase families and show differences in substrate specificity and biocatalytic potential. Bacterial aminoacylases capable of synthesis have been isolated from Burkholderia, Mycolicibacterium, and Streptomyces. Although several proteases and peptidases from S. griseus have been described, no aminoacylases from this species have been identified yet. In this study, we investigated two novel enzymes produced by S. griseus DSM 40236ᵀ . We identified and cloned the respective genes and recombinantly expressed an α-aminoacylase (EC 3.5.1.14), designated SgAA, and an ε-lysine acylase (EC 3.5.1.17), designated SgELA, in S. lividans TK23. The purified aminoacylase SgAA was biochemically characterized, focusing on its hydrolytic activity to determine temperature- and pH optima and stabilities. The aminoacylase could hydrolyze various acetyl-amino acids at the Nα -position with a broad specificity regarding the sidechain. Substrates with longer acyl chains, like lauroyl-amino acids, were hydrolyzed to a lesser extent. Purified aminoacylase SgELA specific for the hydrolysis of Nε -acetyl-L-lysine was unstable and lost its enzymatic activity upon storage for a longer period but could initially be characterized. The pH optimum of SgELA was pH 8.0. While synthesis of acyl-amino acids was not observed with SgELA, SgAA catalyzed the synthesis of lauroyl-methionine.}, language = {en} } @article{MuesgenanntKoersMcNeilRadchenkoetal.2023, author = {Mues genannt Koers, Lucas and McNeil, S. W. and Radchenko, V. and Paulßen, Elisabeth and Hoehr, Cornelia}, title = {Production of Co-58m in a siphon-style liquid target on a medical cyclotron}, volume = {195}, number = {Art. 110734}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0969-8043}, doi = {10.1016/j.apradiso.2023.110734}, year = {2023}, abstract = {We present the production of 58mCo on a small, 13 MeV medical cyclotron utilizing a siphon style liquid target system. Different concentrated iron(III)-nitrate solutions of natural isotopic distribution were irradiated at varying initial pressures and subsequently separated by solid phase extraction chromatography. The radio cobalt (58m/gCo and 56Co) was successfully produced with saturation activities of (0.35 ± 0.03) MBq μA-1 for 58mCo with a separation recovery of (75 ± 2) \% of cobalt after one separation step utilizing LN-resin.}, language = {en} } @article{HafidiElHatkaSchmitzetal.2024, author = {Hafidi, Youssef and El Hatka, Hicham and Schmitz, Dominik and Krauss, Manuel and Pettrak, J{\"u}rgen and Biel, Markus and Ittobane, Najim}, title = {Sustainable soil additives for water and micronutrient supply: swelling and chelating properties of polyaspartic acid hydrogels utilizing newly developed crosslinkers}, series = {Gels}, volume = {10}, journal = {Gels}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {2310-2861}, doi = {10.3390/gels10030170}, pages = {Artikel 170}, year = {2024}, abstract = {Drought and water shortage are serious problems in many arid and semi-arid regions. This problem is getting worse and even continues in temperate climatic regions due to climate change. To address this problem, the use of biodegradable hydrogels is increasingly important for the application as water-retaining additives in soil. Furthermore, efficient (micro-)nutrient supply can be provided by the use of tailored hydrogels. Biodegradable polyaspartic acid (PASP) hydrogels with different available (1,6-hexamethylene diamine (HMD) and L-lysine (LYS)) and newly developed crosslinkers based on diesters of glycine (GLY) and (di-)ethylene glycol (DEG and EG, respectively) were synthesized and characterized using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) and regarding their swelling properties (kinetic, absorbency under load (AUL)) as well as biodegradability of PASP hydrogel. Copper (II) and zinc (II), respectively, were loaded as micronutrients in two different approaches: in situ with crosslinking and subsequent loading of prepared hydrogels. The results showed successful syntheses of di-glycine-ester-based crosslinkers. Hydrogels with good water-absorbing properties were formed. Moreover, the developed crosslinking agents in combination with the specific reaction conditions resulted in higher water absorbency with increased crosslinker content used in synthesis (10\% vs. 20\%). The prepared hydrogels are candidates for water-storing soil additives due to the biodegradability of PASP, which is shown in an exemple. The incorporation of Cu(II) and Zn(II) ions can provide these micronutrients for plant growth.}, language = {en} } @article{BerndtZahn1975, author = {Berndt, Heinz and Zahn, Helmut}, title = {Peptide, 99 : Monomere cyclische Cystinpeptidderivate, III ; Synthese der Schafinsulin-A-Kettensequenzen A2-21 und A1-21 als monomere cyclische Dicystinpeptidderivate}, series = {Justus Liebigs Annalen der Chemie}, volume = {1975}, journal = {Justus Liebigs Annalen der Chemie}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1099-0690}, doi = {10.1002/jlac.197519750908}, pages = {1601 -- 1612}, year = {1975}, abstract = {Die Synthese der Sequenzen A2—21 (13) und A1—21 (15) der Schafinsulin-A-Kette als monomere cyclische Dicystinpeptidderivate wird beschrieben. Die intrachenaren Cystinbr{\"u}cken A6—7 und A 11 —20 vermitteln die L{\"o}slichkeit dieser Derivate in Dimethylformamid und erm{\"o}glichen erstmalig die Reindarstellung vollgesch{\"u}tzter Insulin-A-Kettenderivate. Die w{\"a}hrend der Synthese eingesetzten Schutzgruppen lassen sich mittels Trifluoressigs{\"a}ure und 2-Mercapto{\"a}thanol quantitativ entfernen.}, language = {de} } @article{BerndtGattnerZahn1975, author = {Berndt, Heinz and Gattner, Hans-Gregor and Zahn, Helmut}, title = {Semisynthetisches Des-A1-glycin-Schafinsulin}, series = {Biological Chemistry}, volume = {356}, journal = {Biological Chemistry}, number = {2}, publisher = {De Gruyter}, address = {Berlin}, issn = {1437-4315}, doi = {10.1515/bchm2.1975.356.2.1455}, pages = {1469 -- 1472}, year = {1975}, language = {de} } @article{GielenWolfBerndtetal.1979, author = {Gielen, Hans-G{\"u}nther and Wolf, G{\"u}nter and Berndt, Heinz and Zahn, Helmut}, title = {Synthese der Fragmente A1-8, A9-15 und A16-21 der Schafinsulin-A-Kette unter Verwendung des S-tert-Butylmercaptorestes als Thiolschutzgruppe}, series = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, volume = {360}, journal = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, number = {2}, issn = {1437-4315}, doi = {10.1515/bchm2.1979.360.2.1535}, pages = {1535 -- 1548}, year = {1979}, language = {de} } @article{WolfBerndtBrandenburg1979, author = {Wolf, Wilhelm and Berndt, Heinz and Brandenburg, Dietrich}, title = {Synthese von Fragmenten einer [LysA13] Rinder-Insulin-A-Kette unter Verwendung des S-tert-Butylmercaptorestes als Thiolschutz}, series = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, volume = {360}, journal = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, number = {2}, issn = {1437-4315}, doi = {10.1515/bchm2.1979.360.2.1549}, pages = {1549 -- 1558}, year = {1979}, language = {de} } @article{WilhelmBerndtBrandenburg1979, author = {Wilhelm, Wolff and Berndt, Heinz and Brandenburg, Dietrich}, title = {Zur Synthese der H{\"u}hnerinsulin-A-Kette, I : Darstellung der Fragmente A1-8, A9-15, A1-7 und A8-15}, series = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, volume = {360}, journal = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, number = {2}, issn = {1437-4315}, doi = {10.1515/bchm2.1979.360.2.1559}, pages = {1559 -- 1568}, year = {1979}, language = {de} } @article{Berndt1979, author = {Berndt, Heinz}, title = {Synthese der Sequenz 71—86 des Humanproinsulins, III : Synthese {\"u}ber die Fragmente 71—78 und 79—86}, series = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, volume = {360}, journal = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, number = {1}, issn = {1437-4315}, doi = {10.1515/bchm2.1979.360.1.765}, pages = {765 -- 772}, year = {1979}, language = {de} } @article{OehlenschlaegerVolkmarStiefelmaieretal.2024, author = {Oehlenschl{\"a}ger, Katharina and Volkmar, Marianne and Stiefelmaier, Judith and Langsdorf, Alexander and Holtmann, Dirk and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {New insights into the influence of pre-culture on robust solvent production of C. acetobutylicum}, series = {Applied Microbiology and Biotechnology}, volume = {108}, journal = {Applied Microbiology and Biotechnology}, publisher = {Springer}, address = {Berlin, Heidelberg}, issn = {1432-0614}, doi = {10.1007/s00253-023-12981-8}, pages = {10 Seiten}, year = {2024}, abstract = {Clostridia are known for their solvent production, especially the production of butanol. Concerning the projected depletion of fossil fuels, this is of great interest. The cultivation of clostridia is known to be challenging, and it is difficult to achieve reproducible results and robust processes. However, existing publications usually concentrate on the cultivation conditions of the main culture. In this paper, the influence of cryo-conservation and pre-culture on growth and solvent production in the resulting main cultivation are examined. A protocol was developed that leads to reproducible cultivations of Clostridium acetobutylicum. Detailed investigation of the cell conservation in cryo-cultures ensured reliable cell growth in the pre-culture. Moreover, a reason for the acid crash in the main culture was found, based on the cultivation conditions of the pre-culture. The critical parameter to avoid the acid crash and accomplish the shift to the solventogenesis of clostridia is the metabolic phase in which the cells of the pre-culture were at the time of inoculation of the main culture; this depends on the cultivation time of the pre-culture. Using cells from the exponential growth phase to inoculate the main culture leads to an acid crash. To achieve the solventogenic phase with butanol production, the inoculum should consist of older cells which are in the stationary growth phase. Considering these parameters, which affect the entire cultivation process, reproducible results and reliable solvent production are ensured.}, language = {en} } @article{KruegerGroetzingerBerndt1987, author = {Kr{\"u}ger, G{\"o}tz and Gr{\"o}tzinger, Joachim and Berndt, Heinz}, title = {Enantiomeric resolution of amino acid derivatives on chiral stationary phases by high-performance liquid chromatography}, series = {Journal of Chromatography A}, volume = {1987}, journal = {Journal of Chromatography A}, number = {397}, issn = {0021-9673}, doi = {10.1016/S0021-9673(01)85005-6}, pages = {223 -- 232}, year = {1987}, language = {en} } @article{NokiharaBerndt1978, author = {Nokihara, Kiyoshi and Berndt, Heinz}, title = {Synthesis of hapten-polypeptide conjugates as antigen models for the N-terminal region of the α-2-chain of rabbit skin collagen}, series = {Journal of the Royal Society of Chemistry: Perkin Transactions 1}, volume = {1978}, journal = {Journal of the Royal Society of Chemistry: Perkin Transactions 1}, number = {3}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1364-5463}, doi = {10.1039/P19780000260}, pages = {260 -- 263}, year = {1978}, abstract = {Synthesis of derivatives of the peptide sequence L-pyroglutamyl-L-phenylalanyl-L-aspartyl-glycyl-L-lysyl-glycyl-glycyl-glycine as the antigenic determinant representing the N-terminal non-helical region of the α-2-chain of rabbit skin collagen, and conjugation to two different polypeptide carriers, are described.}, language = {en} } @article{ScheerKapelyukhRodeetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland}, title = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines}, series = {Molecular Pharmacology}, volume = {82}, journal = {Molecular Pharmacology}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.112.080036}, pages = {1022 -- 1029}, year = {2012}, abstract = {Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.}, language = {en} } @article{KalbeKuropkaMeyerStorketal.1988, author = {Kalbe, Jochen and Kuropka, Rolf and Meyer-Stork, L. Sebastian and Berndt, Heinz and [u.a.],}, title = {Isolation and characterization of high-molecular mass DNA from hair shafts}, series = {Biological chemistry}, volume = {369}, journal = {Biological chemistry}, number = {1}, isbn = {0177-3593}, doi = {10.1515/bchm3.1988.369.1.413}, pages = {413 -- 416}, year = {1988}, language = {en} } @article{Berndt1980, author = {Berndt, Heinz}, title = {Zur Reaktion von Iminodithiocarbonaten mit Carbons{\"a}uren. I : Synthese des Modellpeptid-Derivates Z-(L)-Ala-(L/D)-Phe-(L)-Val-OMe}, series = {Tetrahedron letters}, volume = {21}, journal = {Tetrahedron letters}, number = {34}, issn = {0040-4039}, doi = {10.1016/S0040-4039(00)78663-1}, pages = {3265 -- 3268}, year = {1980}, language = {de} } @article{BerndtKrueger1985, author = {Berndt, Heinz and Kr{\"u}ger, G{\"o}tz}, title = {Resolution of enantiomeric amino acid derivatives by high-performance liquid chromatography on chiral stationary phases}, series = {Journal of chromatography A}, volume = {1985}, journal = {Journal of chromatography A}, number = {348}, issn = {0021-9673}, doi = {10.1016/S0021-9673(01)92461-6}, pages = {275 -- 279}, year = {1985}, language = {en} } @article{MeyerStorkKalbeKuropkaetal.1988, author = {Meyer-Stork, L. Sebastian and Kalbe, Jochen and Kuropka, Rolf and Sauter, S. L. and H{\"o}cker, Hartwig and Berndt, Heinz}, title = {Eindeutige Provenienzanalyse von Wolle und feinen Tierhaaren mit Hilfe der Erbsubstanz (DNS)}, series = {Textilveredlung : schweizerische Zeitschrift f{\"u}r Textilchemie, Textilveredlung und deren Randgebiete}, volume = {23}, journal = {Textilveredlung : schweizerische Zeitschrift f{\"u}r Textilchemie, Textilveredlung und deren Randgebiete}, number = {9}, issn = {0040-5310}, pages = {304 -- 307}, year = {1988}, language = {de} } @article{SchnabelSchnabelBerndt1971, author = {Schnabel, Eugen and Schnabel, Henning and Berndt, Heinz}, title = {Zur selektiven acidolytischen Abspaltbarkeit der tert.-Butyloxycarbonyl-Gruppe}, series = {Justus Liebigs Annalen der Chemie}, volume = {749}, journal = {Justus Liebigs Annalen der Chemie}, number = {1}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1099-0690}, doi = {10.1002/jlac.19717490111}, pages = {90 -- 108}, year = {1971}, abstract = {Die tert.-Butyloxycarbonyl-Gruppe (Boc) l{\"a}ßt sich mittels reiner Trifluoressigs{\"a}ure nicht selektiv neben dem Benzyloxycarbonyl-Rest (Z) abspalten. Das gelingt auch nicht mit L{\"o}sungen von Trifluoressigs{\"a}ure bzw. Chlorwasserstoff in organischen L{\"o}sungsmitteln. Kern-substituierte Z-Gruppen wie Z(pCl), Z(mCl) oder Z(pNO₂) sind zwar stabiler, werden aber von den obengenannten Reagenzien ebenfalls angegriffen bzw. sind nicht mehr acidolytisch abspaltbar. - Mit 70proz. w{\"a}ßriger Trifluoressigs{\"a}ure gelingt die Abspaltung von Boc neben Z dagegen fast selektiv; dabei werden aber Benzylester, besonders Glutamins{\"a}ure-γ-benzylester, teilweise hydrolysiert, w{\"a}hrend Methyl- sowie {\"A}thylester nahezu best{\"a}ndig sind. Die Brauchbarkeit des Abspaltungsverfahrens wird anhand der schrittweise durchgef{\"u}hrten Synthese zweier Heptapeptid-Derivate gezeigt. - {\"A}hnlich spezifisch gelingt die Abspaltung von Boc mit Bortrifluorid-{\"a}therat in Eisessig; Benzylester sind gegen{\"u}ber diesem Reagenz stabiler als gegen w{\"a}ßrige Trifluoressigs{\"a}ure. Das Bortrifluorid-Verfahren eignet sich besonders f{\"u}r die Abspaltung von Boc-Gruppen neben s{\"a}urelabilen Thiol-Schutzgruppen (Tetrahydropyranyl- bzw. Trityl-Rest) sowie neben dem Cyclocystinyl-Rest. Die Leistungsf{\"a}higkeit der Methode wird durch die Synthese zweier Peptid-Derivate mit S-Trityl-Schutzgruppen belegt. Als Nebenreaktion ist die Acetylierung von aliphatischen Hydroxylgruppen m{\"o}glich. Sie l{\"a}ßt sich vermeiden, wenn man die Spaltung in anderen L{\"o}sungsmitteln durchf{\"u}hrt. Die als Modellverbindungen f{\"u}r Stabilit{\"a}tsuntersuchungen verwendeten Nε-acylierten Lysin-Derivate werden mit dem Aminos{\"a}ureanalysator quantitativ neben Lysin bestimmt.}, language = {de} } @article{KuropkaMuellerHoeckeretal.1989, author = {Kuropka, Rolf and M{\"u}ller, Bettina and H{\"o}cker, Hartwig and Berndt, Heinz}, title = {Chiral stationary phases via hydrosilylation reaction of N-acryloylamino acids : I. Stationary phase with one chiral centre for high-performance liquid chromatography and development of a new derivatization pattern for amino acid enantiomers}, series = {Journal of chromatography A}, journal = {Journal of chromatography A}, number = {481}, isbn = {0021-9673}, pages = {380 -- 386}, year = {1989}, language = {en} } @article{NokiharaBerndt1978, author = {Nokihara, Kiyoshi and Berndt, Heinz}, title = {Studies on sulfur-containing peptides : tert-butyloxycarbonylsulfenyl and benzyloxycarbonylsulfenyl derivatives as protecting groups for cysteine}, series = {The journal of organic chemistry}, volume = {43}, journal = {The journal of organic chemistry}, number = {25}, publisher = {American Chemical Society}, address = {Washington}, issn = {0022-3263}, doi = {10.1021/jo00419a046}, pages = {4893 -- 4895}, year = {1978}, language = {en} } @article{KalbeHoeckerBerndt1989, author = {Kalbe, Jochen and H{\"o}cker, Hartwig and Berndt, Heinz}, title = {Design of enzyme reactors as chromatographic columns for racemic resolution of amino acid esters}, series = {Chromatographia}, volume = {28}, journal = {Chromatographia}, number = {3-4}, isbn = {0009-5893}, doi = {10.1007/BF02319646}, pages = {193 -- 196}, year = {1989}, language = {en} } @article{TurckBerndt1981, author = {Turck, Christoph W. and Berndt, Heinz}, title = {Synthese definierter Peptid-Derivate durch Aminolyse von 3-(Nα-Acyl-peptidyloxy)-2-hydroxy-N-alkylbenzamiden bei erh{\"o}hten Temperaturen, I : Synthese des Modellpeptid-Derivates Z-Ala-Phe-Gly-N(Et)2}, series = {Hoppe-Seyler´s Zeitschrift f{\"u}r physiologische Chemie}, volume = {362}, journal = {Hoppe-Seyler´s Zeitschrift f{\"u}r physiologische Chemie}, number = {1}, issn = {1437-4315}, doi = {10.1515/bchm2.1981.362.1.821}, pages = {821 -- 828}, year = {1981}, language = {de} }