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Papers by Timo Niedermeyer

Research paper thumbnail of Novel Penicillins Synthesized by Biotransformation Using Laccase from Trametes spec

Chemical & Pharmaceutical Bulletin, 2006

Eight novel penicillins were synthesized by heteromolecular reaction of ampicillin or amoxicillin... more Eight novel penicillins were synthesized by heteromolecular reaction of ampicillin or amoxicillin with 2,5-dihydroxybenzoic acid derivatives using a laccase from Trametes spec. All products inhibited the growth of several gram positive bacterial strains in the agar diffusion assay, among them methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. The products protected mice against an infection with Staphylococcus aureus lethal to the untreated animals. Cytotoxicity and acute toxicity of the new compounds were neglectable. The results show the usefulness of laccase for the synthesis of potential new antibiotics. The biological activity of the new compounds stimulates intensified pharmacological tests.

Research paper thumbnail of Nuclear Amination Catalyzed by Fungal Laccases: Reaction Products of p -Hydroquinones and Primary Aromatic Amines

Journal of Organic Chemistry, 2005

Research paper thumbnail of Novel Cephalosporins Synthesized by Amination of 2,5-Dihydroxybenzoic Acid Derivatives Using Fungal Laccases II

Chemical & Pharmaceutical Bulletin, 2007

Research paper thumbnail of Nuclear Amination Catalyzed by Fungal Laccases: Reaction Products of p-Hydroquinones and Primary Aromatic Amines

Cheminform, 2005

For Abstract see ChemInform Abstract in Full Text.

Research paper thumbnail of The Pharmacological Potential of Mushrooms

This review describes pharmacologically active compounds from mushrooms. Compounds and complex su... more This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.

Research paper thumbnail of Nuclear amination catalyzed by fungal laccases: Comparison of laccase catalyzed amination with known chemical routes to aminoquinones

Journal of Molecular Catalysis B-enzymatic, 2007

Research paper thumbnail of Antiviral Terpenoid Constituents of Ganoderma p feifferi

Antiviral Terpenoid Constituents of Ganoderma p feifferi

Journal of Natural Products, 2005

Four sterols and 10 triterpenes were isolated from the fruiting bodies of Ganoderma pfeifferi, in... more Four sterols and 10 triterpenes were isolated from the fruiting bodies of Ganoderma pfeifferi, including the three new triterpenes 3,7,11-trioxo-5alpha-lanosta-8,24-diene-26-al (lucialdehyde D, 1), 5alpha-lanosta-8,24-diene-26-hydroxy-3,7-dione (ganoderone A, 2), and 5alpha-lanosta-8-ene-24,25-epoxy-26-hydroxy-3,7-dione (ganoderone C, 3). The structures of 1-3 were determined on the basis of spectroscopic evidence. Antibacterial, antifungal, and antiviral activity were studied for some of the isolated compounds. Ganoderone A (2), lucialdehyde B (4), and ergosta-7,22-dien-3beta-ol (7) were found to exhibit potent inhibitory activity against herpes simplex virus.

Research paper thumbnail of Laccase-induced cross-coupling of 4-aminobenzoic acid with para-dihydroxylated compounds 2,5-dihydroxy- N-(2-hydroxyethyl)-benzamide and 2,5-dihydroxybenzoic acid methyl ester

Laccase-induced cross-coupling of 4-aminobenzoic acid with para-dihydroxylated compounds 2,5-dihydroxy- N-(2-hydroxyethyl)-benzamide and 2,5-dihydroxybenzoic acid methyl ester

Journal of Molecular Catalysis B-enzymatic, 2005

A fungal laccase from Trametes villosa (EC 1.10.3.2 p-phenoloxidase) was used to mediate the oxid... more A fungal laccase from Trametes villosa (EC 1.10.3.2 p-phenoloxidase) was used to mediate the oxidation and cross-coupling of two para-dihydroxylated benzoic acid derivatives with 4-aminobenzoic acid. The incubation of 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide and 4-aminobenzoic acid with laccase under oxygen conditions resulted in the formation of 2-(4′-carboxy-anilino)-N-(2″-hydroxyethyl)-3,6-dioxo-1,4-cyclohexadien-1-carboxamide as the main product (yield>85%). When 2,5-dihydroxybenzoic acid methyl ester was a co-substrate of 4-aminobenzoic acid, 2-(4′-carboxy-anilino)-N-(2″-hydroxyethyl)-3,6-dioxo-1,4-cyclohexadien-1-carboxy methyl ester was produced (yield>75%). Both products were N–C coupling dimers consisting of para-quinone and benzoic acid moieties. The formation of quinone structures in the presence of T. villosa laccase may be useful in pharmaceutical synthesis. Because of high product yields and low amount of by-products laccase of T. villosa seems to be a suitable enzyme among laccases acting at pH 5 for the synthesis of heterologous dimers.

Research paper thumbnail of Isolation of Microcystins from the Cyanobacterium Planktothrix rubescens Strain No80

Three minor microcystins have been isolated from a Planktothrix rubescens strain. Their structure... more Three minor microcystins have been isolated from a Planktothrix rubescens strain. Their structures have been elucidated by one-and two-dimensional NMR spectroscopy and high-resolution tandem mass spectrometry as the compounds [Asp 3 ,(E)-Dhb 7 ]MC-LY (1), [Asp 3 ,(E)-Dhb 7 ]MC-HtyW (2), and [Asp 3 ,(E)-Dhb 7 ]MC-LW (3). The amino acids found at the variable positions 2 and 4 of the microcystin core structure are in accordance with the predicted amino acid substrate activation selectivities of the non-ribosomal peptide synthetases McyA and McyB described earlier for this strain.

Research paper thumbnail of Lindequist, Niedermeyer, Jülich 2005 The pharmacological potential of mushrooms

This review describes pharmacologically active compounds from mushrooms. Compounds and complex su... more This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.

Research paper thumbnail of Selectivity and Potency of Microcystin Congeners against OATP1B1 and OATP1B3 Expressing Cancer Cells Editor

Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport... more Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC 50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs. Citation: Niedermeyer THJ, Daily A, Swiatecka-Hagenbruch M, Moscow JA (2014) Selectivity and Potency of Microcystin Congeners against OATP1B1 and OATP1B3 Expressing Cancer Cells. PLoS ONE 9(3): e91476.

Research paper thumbnail of Niedermeyer et al. 2013 Isolation of farnesylhydroquinones from the basidiomycete Ganoderma pfeifferi

Two farnesylhydroquinones were isolated from the fruiting bodies of Ganoderma pfeifferi, farnesyl... more Two farnesylhydroquinones were isolated from the fruiting bodies of Ganoderma pfeifferi, farnesylhydroquinone (1) and the new compound ganomycin K (2), (5S)-3-[(E)-7,8-dihydroxy-4,8-dimethylnon-3-enyl]-5-(2,5-dihydroxyphenyl)-furan-2(5H)one. The structures of 1 and 2 were determined on the basis of mass spectrometric and NMR spectroscopic evidence. The antibacterial activity of the isolated compounds was neglectable.

Research paper thumbnail of Niedermeyer, Strohalm 2012 m Mass as a software tool for the annotation of cyclic peptide tandem mass spectra

Natural or synthetic cyclic peptides often possess pronounced bioactivity. Their mass spectrometr... more Natural or synthetic cyclic peptides often possess pronounced bioactivity. Their mass spectrometric characterization is difficult due to the predominant occurrence of non-proteinogenic monomers and the complex fragmentation patterns observed. Even though several software tools for cyclic peptide tandem mass spectra annotation have been published, these tools are still unable to annotate a majority of the signals observed in experimentally obtained mass spectra. They are thus not suitable for extensive mass spectrometric characterization of these compounds. This lack of advanced and userfriendly software tools has motivated us to extend the fragmentation module of a freely available open-source software, mMass (http://www.mmass.org), to allow for cyclic peptide tandem mass spectra annotation and interpretation. The resulting software has been tested on several cyanobacterial and other naturally occurring peptides. It has been found to be superior to other currently available tools concerning both usability and annotation extensiveness. Thus it is highly useful for accelerating the structure confirmation and elucidation of cyclic as well as linear peptides and depsipeptides.

Research paper thumbnail of Novel Penicillins Synthesized by Biotransformation Using Laccase from Trametes spec

Chemical & Pharmaceutical Bulletin, 2006

Eight novel penicillins were synthesized by heteromolecular reaction of ampicillin or amoxicillin... more Eight novel penicillins were synthesized by heteromolecular reaction of ampicillin or amoxicillin with 2,5-dihydroxybenzoic acid derivatives using a laccase from Trametes spec. All products inhibited the growth of several gram positive bacterial strains in the agar diffusion assay, among them methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. The products protected mice against an infection with Staphylococcus aureus lethal to the untreated animals. Cytotoxicity and acute toxicity of the new compounds were neglectable. The results show the usefulness of laccase for the synthesis of potential new antibiotics. The biological activity of the new compounds stimulates intensified pharmacological tests.

Research paper thumbnail of Nuclear Amination Catalyzed by Fungal Laccases: Reaction Products of p -Hydroquinones and Primary Aromatic Amines

Journal of Organic Chemistry, 2005

Research paper thumbnail of Novel Cephalosporins Synthesized by Amination of 2,5-Dihydroxybenzoic Acid Derivatives Using Fungal Laccases II

Chemical & Pharmaceutical Bulletin, 2007

Research paper thumbnail of Nuclear Amination Catalyzed by Fungal Laccases: Reaction Products of p-Hydroquinones and Primary Aromatic Amines

Cheminform, 2005

For Abstract see ChemInform Abstract in Full Text.

Research paper thumbnail of The Pharmacological Potential of Mushrooms

This review describes pharmacologically active compounds from mushrooms. Compounds and complex su... more This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.

Research paper thumbnail of Nuclear amination catalyzed by fungal laccases: Comparison of laccase catalyzed amination with known chemical routes to aminoquinones

Journal of Molecular Catalysis B-enzymatic, 2007

Research paper thumbnail of Antiviral Terpenoid Constituents of Ganoderma p feifferi

Antiviral Terpenoid Constituents of Ganoderma p feifferi

Journal of Natural Products, 2005

Four sterols and 10 triterpenes were isolated from the fruiting bodies of Ganoderma pfeifferi, in... more Four sterols and 10 triterpenes were isolated from the fruiting bodies of Ganoderma pfeifferi, including the three new triterpenes 3,7,11-trioxo-5alpha-lanosta-8,24-diene-26-al (lucialdehyde D, 1), 5alpha-lanosta-8,24-diene-26-hydroxy-3,7-dione (ganoderone A, 2), and 5alpha-lanosta-8-ene-24,25-epoxy-26-hydroxy-3,7-dione (ganoderone C, 3). The structures of 1-3 were determined on the basis of spectroscopic evidence. Antibacterial, antifungal, and antiviral activity were studied for some of the isolated compounds. Ganoderone A (2), lucialdehyde B (4), and ergosta-7,22-dien-3beta-ol (7) were found to exhibit potent inhibitory activity against herpes simplex virus.

Research paper thumbnail of Laccase-induced cross-coupling of 4-aminobenzoic acid with para-dihydroxylated compounds 2,5-dihydroxy- N-(2-hydroxyethyl)-benzamide and 2,5-dihydroxybenzoic acid methyl ester

Laccase-induced cross-coupling of 4-aminobenzoic acid with para-dihydroxylated compounds 2,5-dihydroxy- N-(2-hydroxyethyl)-benzamide and 2,5-dihydroxybenzoic acid methyl ester

Journal of Molecular Catalysis B-enzymatic, 2005

A fungal laccase from Trametes villosa (EC 1.10.3.2 p-phenoloxidase) was used to mediate the oxid... more A fungal laccase from Trametes villosa (EC 1.10.3.2 p-phenoloxidase) was used to mediate the oxidation and cross-coupling of two para-dihydroxylated benzoic acid derivatives with 4-aminobenzoic acid. The incubation of 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide and 4-aminobenzoic acid with laccase under oxygen conditions resulted in the formation of 2-(4′-carboxy-anilino)-N-(2″-hydroxyethyl)-3,6-dioxo-1,4-cyclohexadien-1-carboxamide as the main product (yield>85%). When 2,5-dihydroxybenzoic acid methyl ester was a co-substrate of 4-aminobenzoic acid, 2-(4′-carboxy-anilino)-N-(2″-hydroxyethyl)-3,6-dioxo-1,4-cyclohexadien-1-carboxy methyl ester was produced (yield>75%). Both products were N–C coupling dimers consisting of para-quinone and benzoic acid moieties. The formation of quinone structures in the presence of T. villosa laccase may be useful in pharmaceutical synthesis. Because of high product yields and low amount of by-products laccase of T. villosa seems to be a suitable enzyme among laccases acting at pH 5 for the synthesis of heterologous dimers.

Research paper thumbnail of Isolation of Microcystins from the Cyanobacterium Planktothrix rubescens Strain No80

Three minor microcystins have been isolated from a Planktothrix rubescens strain. Their structure... more Three minor microcystins have been isolated from a Planktothrix rubescens strain. Their structures have been elucidated by one-and two-dimensional NMR spectroscopy and high-resolution tandem mass spectrometry as the compounds [Asp 3 ,(E)-Dhb 7 ]MC-LY (1), [Asp 3 ,(E)-Dhb 7 ]MC-HtyW (2), and [Asp 3 ,(E)-Dhb 7 ]MC-LW (3). The amino acids found at the variable positions 2 and 4 of the microcystin core structure are in accordance with the predicted amino acid substrate activation selectivities of the non-ribosomal peptide synthetases McyA and McyB described earlier for this strain.

Research paper thumbnail of Lindequist, Niedermeyer, Jülich 2005 The pharmacological potential of mushrooms

This review describes pharmacologically active compounds from mushrooms. Compounds and complex su... more This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.

Research paper thumbnail of Selectivity and Potency of Microcystin Congeners against OATP1B1 and OATP1B3 Expressing Cancer Cells Editor

Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport... more Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC 50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs. Citation: Niedermeyer THJ, Daily A, Swiatecka-Hagenbruch M, Moscow JA (2014) Selectivity and Potency of Microcystin Congeners against OATP1B1 and OATP1B3 Expressing Cancer Cells. PLoS ONE 9(3): e91476.

Research paper thumbnail of Niedermeyer et al. 2013 Isolation of farnesylhydroquinones from the basidiomycete Ganoderma pfeifferi

Two farnesylhydroquinones were isolated from the fruiting bodies of Ganoderma pfeifferi, farnesyl... more Two farnesylhydroquinones were isolated from the fruiting bodies of Ganoderma pfeifferi, farnesylhydroquinone (1) and the new compound ganomycin K (2), (5S)-3-[(E)-7,8-dihydroxy-4,8-dimethylnon-3-enyl]-5-(2,5-dihydroxyphenyl)-furan-2(5H)one. The structures of 1 and 2 were determined on the basis of mass spectrometric and NMR spectroscopic evidence. The antibacterial activity of the isolated compounds was neglectable.

Research paper thumbnail of Niedermeyer, Strohalm 2012 m Mass as a software tool for the annotation of cyclic peptide tandem mass spectra

Natural or synthetic cyclic peptides often possess pronounced bioactivity. Their mass spectrometr... more Natural or synthetic cyclic peptides often possess pronounced bioactivity. Their mass spectrometric characterization is difficult due to the predominant occurrence of non-proteinogenic monomers and the complex fragmentation patterns observed. Even though several software tools for cyclic peptide tandem mass spectra annotation have been published, these tools are still unable to annotate a majority of the signals observed in experimentally obtained mass spectra. They are thus not suitable for extensive mass spectrometric characterization of these compounds. This lack of advanced and userfriendly software tools has motivated us to extend the fragmentation module of a freely available open-source software, mMass (http://www.mmass.org), to allow for cyclic peptide tandem mass spectra annotation and interpretation. The resulting software has been tested on several cyanobacterial and other naturally occurring peptides. It has been found to be superior to other currently available tools concerning both usability and annotation extensiveness. Thus it is highly useful for accelerating the structure confirmation and elucidation of cyclic as well as linear peptides and depsipeptides.