The Experts below are selected from a list of 75525 Experts worldwide ranked by ideXlab platform

Axel Zeeck - One of the best experts on this subject based on the ideXlab platform.

Randall T. Peterson - One of the best experts on this subject based on the ideXlab platform.

  • Chemical Screening in Zebrafish
    Methods in molecular biology (Clifton N.J.), 2016
    Co-Authors: Colleen A. Brady, Andrew J. Rennekamp, Randall T. Peterson
    Abstract:

    Phenotypic small molecule screens in zebrafish have gained popularity as an unbiased approach to probe biological processes. In this chapter we outline basic methods for performing Chemical screens with larval zebrafish including breeding large numbers of embryos, plating larval fish into multi-well dishes, and adding small molecules to these wells. We also highlight important considerations when designing and interpreting the results of a phenotypic screen and possible follow-up approaches, including popular methods used to identify the mechanism of action of a Chemical compound.

  • 15 years of zebrafish Chemical Screening
    Current Opinion in Chemical Biology, 2015
    Co-Authors: Andrew J. Rennekamp, Randall T. Peterson
    Abstract:

    In 2000, the first Chemical screen using living zebrafish in a multi-well plate was reported. Since then, more than 60 additional screens have been published describing whole-organism drug and pathway discovery projects in zebrafish. To investigate the scope of the work reported in the last 14 years and to identify trends in the field, we analyzed the discovery strategies of 64 primary research articles from the literature. We found that zebrafish screens have expanded beyond the use of developmental phenotypes to include behavioral, cardiac, metabolic, proliferative and regenerative endpoints. Additionally, many creative strategies have been used to uncover the mechanisms of action of new small molecules including Chemical phenocopy, genetic phenocopy, mutant rescue, and spatial localization strategies.

Russell G. Kerr - One of the best experts on this subject based on the ideXlab platform.

Ralf Thiericke - One of the best experts on this subject based on the ideXlab platform.

  • Secondary Metabolites by Chemical Screening, 29.
    Liebigs Annalen, 2006
    Co-Authors: Axel Göhrt, Susanne Grabley, Ralf Thiericke, Axel Zeeck
    Abstract:

    Novel pyranacetals, named agistatines A, B, D, and E (1 to 4), were discovered by a Chemical Screening in the culture broth of the fungus FH-A 6239. The structures were established by detailed spectroscopic investigations and confirmed by X-ray analysis of agistatine B (2), 4-O-(2-bromobenzoyl)dihydroagistatine A (6), 4-O-(2-bromobenzoyl)agistatine B (7), and agistatine E (4) leading to the stereoChemical information. The described secondary metabolites exhibit unusual bicyclic (1 and 3) and tricyclic (2 and 4) structures with a characteristic ketal moiety at C-2 (except 3). The instability of the main fermentation product agistatine E (4) is caused by an additional hemiketal located at the adjacent C--8a.

  • Jenamidines A to C: unusual alkaloids from Streptomyces sp. with specific antiproliferative properties obtained by Chemical Screening.
    The Journal of antibiotics, 2003
    Co-Authors: Dirk Wunderlich, Susanne Grabley, Ralf Thiericke, Hans-martin Dahse, Xiao-zhang Feng, Isabel Sattler
    Abstract:

    Three new naturally occurring bicyclic alkaloids, jenamidines A (1), B (2) and C (3), were discovered and isolated from the culture broth of Streptomyces sp. (strain HKI0297) via the Chemical Screening approach. Fermentation, isolation, structure and biological activities of these three new secondary metabolites are reported. The jenamidines have an unusual octahydro-pyrido[1,2-a]pyrimidine skeleton. Jenamidine A (1) shows antiproliferative effects against the chronic myeloid leukaemic cell line K-562. In addition, the new tricyclic sesquiterpenoid, africantriol (4) was isolated from the same strain.

  • Biomolecular-Chemical Screening: a novel Screening approach for the discovery of biologically active secondary metabolites. I. Screening strategy and validation.
    The Journal of antibiotics, 1999
    Co-Authors: Armin Maier, Susanne Grabley, Corinna Maul, Marion Zerlin, Isabel Sattler, Ralf Thiericke
    Abstract:

    Chemical Screening using thin-layer chromatography and various staining reagents offers the opportunity to visualize an almost complete picture of a microbial secondary metabolite pattern (metabolic finger-print). A thorough application of this strategy resulted in a number of biologically active new secondary metabolites, although the Screening strategy is per se not correlated to any biological activity. In the present paper we report on a novel approach called biomolecular-Chemical Screening which combines the Chemical Screening strategy with binding studies of biological relevance. Making use of thin-layer chromatography (TLC) and subsequent staining, biomolecular-Chemical Screening allows to examine binding properties of low molecular weight metabolites to certain bio-macromolecules. The Screening strategy itself, as well as independent validation of the results using DNA as selected bio-macromolecule are presented. The biomolecular-Chemical Screening method is useful to screen binding behaviour towards DNA of both, pure metabolites by one-dimensional TLC, and crude extracts by two-dimensional TLC. Investigation of pure secondary metabolites as well as Screening of crude microbial extracts and new secondary metabolites obtained with this Screening strategy are presented in accompanying papers.

  • Biomolecular-Chemical Screening: a novel Screening approach for the discovery of biologically active secondary metabolites. II. Application studies with pure metabolites.
    The Journal of antibiotics, 1999
    Co-Authors: Armin Maier, Susanne Grabley, Corinna Maul, Marion Zerlin, Ralf Thiericke
    Abstract:

    The novel Screening strategy called "biomolecular-Chemical Screening" combines the advantages of the Chemical Screening approach--the analysis of the chromatographic and Chemical behaviour of secondary metabolites on TLC plates--with binding studies of these molecules with bio-macromolecules like DNA. This approach was advantageously used to detect the interaction of pure compounds with DNA. In order to prove the reliability of the biomolecular-Chemical Screening and to examine DNA-binding properties, 470 pure secondary metabolites were analysed by this method. Besides the confirmation of already known binders with the TLC-based method, for a number of natural products DNA-binding properties were discovered for the first time. In consequence, binding of pure compounds can be measured by 1D TLC in a reliable and easy manner, in which DNA is applied together with the test compound at the starting spot. Analysis is performed via differences in Rf-values in comparison to a reference chromatogram without DNA.

  • Biomolecular-Chemical Screening: A Novel Screening Approach for the Discovery of Biologically Active Secondary Metabolites III. New DNA-binding Metabolites
    The Journal of antibiotics, 1999
    Co-Authors: Corinna Maul, Susanne Grabley, Armin Maier, Marion Zerlin, Isabel Sattler, Claudia Hinze, Corinna Koch, Ralf Thiericke
    Abstract:

    Based on the Chemical Screening technique, biomolecular-Chemical Screening has been developed which makes use of two-dimensional TLC analysis of microbial extracts and combines thin-layer chromatography (RP-18) with binding studies towards DNA. In the first dimension the metabolites of the crude microbial extract are separated, and in the second dimension binding properties towards DNA are analysed. An initial Screening program with 500 microbial extracts prepared by solid-phase extraction with XAD-16 resin resulted in 17 samples which contained metabolites with significant DNA-binding behavior. Fermentation, isolation and structural characterization led to already known metabolites [phenazine-1, 6-dicarboxylate (1), phencomycin (2), 11-carboxy-menoxymycin B (3), soyasaponine I (4), and (8S)-3-(2-hydroxypropyl)-cyclohexanone (5)], as well as to new secondary metabolites. Fermentation of the producing organisms of the new DNA-binding metabolites, ent-8, 8adihydro-ramulosin (6), (2R, 4R)-4-hydroxy-2-(1, 3-pentadienyl)-piperidine (7), (5R)-dihydro-5-pentyl-4'-methyl-4'-hydroxy-2(3H)-furanone (8), and seco-4, 23-hydroxyoleane-12-en-22-one3-carboxylic acid (9), as well as isolation, structural characterization, and physico-Chemical properties are reported.

Susanne Grabley - One of the best experts on this subject based on the ideXlab platform.

  • Secondary Metabolites by Chemical Screening, 29.
    Liebigs Annalen, 2006
    Co-Authors: Axel Göhrt, Susanne Grabley, Ralf Thiericke, Axel Zeeck
    Abstract:

    Novel pyranacetals, named agistatines A, B, D, and E (1 to 4), were discovered by a Chemical Screening in the culture broth of the fungus FH-A 6239. The structures were established by detailed spectroscopic investigations and confirmed by X-ray analysis of agistatine B (2), 4-O-(2-bromobenzoyl)dihydroagistatine A (6), 4-O-(2-bromobenzoyl)agistatine B (7), and agistatine E (4) leading to the stereoChemical information. The described secondary metabolites exhibit unusual bicyclic (1 and 3) and tricyclic (2 and 4) structures with a characteristic ketal moiety at C-2 (except 3). The instability of the main fermentation product agistatine E (4) is caused by an additional hemiketal located at the adjacent C--8a.

  • Jenamidines A to C: unusual alkaloids from Streptomyces sp. with specific antiproliferative properties obtained by Chemical Screening.
    The Journal of antibiotics, 2003
    Co-Authors: Dirk Wunderlich, Susanne Grabley, Ralf Thiericke, Hans-martin Dahse, Xiao-zhang Feng, Isabel Sattler
    Abstract:

    Three new naturally occurring bicyclic alkaloids, jenamidines A (1), B (2) and C (3), were discovered and isolated from the culture broth of Streptomyces sp. (strain HKI0297) via the Chemical Screening approach. Fermentation, isolation, structure and biological activities of these three new secondary metabolites are reported. The jenamidines have an unusual octahydro-pyrido[1,2-a]pyrimidine skeleton. Jenamidine A (1) shows antiproliferative effects against the chronic myeloid leukaemic cell line K-562. In addition, the new tricyclic sesquiterpenoid, africantriol (4) was isolated from the same strain.

  • Biomolecular-Chemical Screening: a novel Screening approach for the discovery of biologically active secondary metabolites. I. Screening strategy and validation.
    The Journal of antibiotics, 1999
    Co-Authors: Armin Maier, Susanne Grabley, Corinna Maul, Marion Zerlin, Isabel Sattler, Ralf Thiericke
    Abstract:

    Chemical Screening using thin-layer chromatography and various staining reagents offers the opportunity to visualize an almost complete picture of a microbial secondary metabolite pattern (metabolic finger-print). A thorough application of this strategy resulted in a number of biologically active new secondary metabolites, although the Screening strategy is per se not correlated to any biological activity. In the present paper we report on a novel approach called biomolecular-Chemical Screening which combines the Chemical Screening strategy with binding studies of biological relevance. Making use of thin-layer chromatography (TLC) and subsequent staining, biomolecular-Chemical Screening allows to examine binding properties of low molecular weight metabolites to certain bio-macromolecules. The Screening strategy itself, as well as independent validation of the results using DNA as selected bio-macromolecule are presented. The biomolecular-Chemical Screening method is useful to screen binding behaviour towards DNA of both, pure metabolites by one-dimensional TLC, and crude extracts by two-dimensional TLC. Investigation of pure secondary metabolites as well as Screening of crude microbial extracts and new secondary metabolites obtained with this Screening strategy are presented in accompanying papers.

  • Biomolecular-Chemical Screening: A Novel Screening Approach for the Discovery of Biologically Active Secondary Metabolites III. New DNA-binding Metabolites
    The Journal of antibiotics, 1999
    Co-Authors: Corinna Maul, Susanne Grabley, Armin Maier, Marion Zerlin, Isabel Sattler, Claudia Hinze, Corinna Koch, Ralf Thiericke
    Abstract:

    Based on the Chemical Screening technique, biomolecular-Chemical Screening has been developed which makes use of two-dimensional TLC analysis of microbial extracts and combines thin-layer chromatography (RP-18) with binding studies towards DNA. In the first dimension the metabolites of the crude microbial extract are separated, and in the second dimension binding properties towards DNA are analysed. An initial Screening program with 500 microbial extracts prepared by solid-phase extraction with XAD-16 resin resulted in 17 samples which contained metabolites with significant DNA-binding behavior. Fermentation, isolation and structural characterization led to already known metabolites [phenazine-1, 6-dicarboxylate (1), phencomycin (2), 11-carboxy-menoxymycin B (3), soyasaponine I (4), and (8S)-3-(2-hydroxypropyl)-cyclohexanone (5)], as well as to new secondary metabolites. Fermentation of the producing organisms of the new DNA-binding metabolites, ent-8, 8adihydro-ramulosin (6), (2R, 4R)-4-hydroxy-2-(1, 3-pentadienyl)-piperidine (7), (5R)-dihydro-5-pentyl-4'-methyl-4'-hydroxy-2(3H)-furanone (8), and seco-4, 23-hydroxyoleane-12-en-22-one3-carboxylic acid (9), as well as isolation, structural characterization, and physico-Chemical properties are reported.

  • Biomolecular-Chemical Screening: a novel Screening approach for the discovery of biologically active secondary metabolites. II. Application studies with pure metabolites.
    The Journal of antibiotics, 1999
    Co-Authors: Armin Maier, Susanne Grabley, Corinna Maul, Marion Zerlin, Ralf Thiericke
    Abstract:

    The novel Screening strategy called "biomolecular-Chemical Screening" combines the advantages of the Chemical Screening approach--the analysis of the chromatographic and Chemical behaviour of secondary metabolites on TLC plates--with binding studies of these molecules with bio-macromolecules like DNA. This approach was advantageously used to detect the interaction of pure compounds with DNA. In order to prove the reliability of the biomolecular-Chemical Screening and to examine DNA-binding properties, 470 pure secondary metabolites were analysed by this method. Besides the confirmation of already known binders with the TLC-based method, for a number of natural products DNA-binding properties were discovered for the first time. In consequence, binding of pure compounds can be measured by 1D TLC in a reliable and easy manner, in which DNA is applied together with the test compound at the starting spot. Analysis is performed via differences in Rf-values in comparison to a reference chromatogram without DNA.