TY  - GEN
A1  - Riano-Pachon, Diego Mauricio
A1  - Nagel, Axel
A1  - Neigenfind, Jost
A1  - Wagner, Robert
A1  - Basekow, Rico
A1  - Weber, Elke
A1  - Müller-Röber, Bernd
A1  - Diehl, Svenja
A1  - Kersten, Birgit
T1  - GabiPD : the GABI primary database - a plant integrative "omics" database
N2  - The GABI Primary Database, GabiPD (http:// www.gabipd.org/), was established in the frame of the German initiative for Genome Analysis of the Plant Biological System (GABI). The goal of GabiPD is to collect, integrate, analyze and visualize primary information from GABI projects. GabiPD constitutes a repository and analysis platform for a wide array of heterogeneous data from high-throughput experiments in several plant species. Data from different ‘omics’ fronts are incorporated (i.e. genomics, transcriptomics, proteomics and metabolomics), originating from 14 different model or crop species. We have developed the concept of GreenCards for textbased retrieval of all data types in GabiPD (e.g. clones, genes, mutant lines). All data types point to a central Gene GreenCard, where gene information is integrated from genome projects or NCBI UniGene sets. The centralized Gene GreenCard allows visualizing ESTs aligned to annotated transcripts as well as displaying identified protein domains and gene structure. Moreover, GabiPD makes available interactive genetic maps from potato and barley, and protein 2DE gels from Arabidopsis thaliana and Brassica napus. Gene expression and metabolic-profiling data can be visualized through MapManWeb. By the integration of complex data in a framework of existing knowledge, GabiPD provides new insights and allows for new interpretations of the data.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 137 
KW  - Phosphorylation sites
KW  - Arabidopsis thaliana
KW  - Information
KW  - Proteins
KW  - Families
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-45075
ER  - 
TY  - JOUR
A1  - Wolff, Martin
A1  - Schüler, Anja
A1  - Gast, Klaus
A1  - Seckler, Robert
A1  - Evers, Andreas
A1  - Pfeiffer-Marek, Stefania
A1  - Kurz, Michael
A1  - Nagel, Norbert
A1  - Haack, Torsten
A1  - Wagner, Michael
A1  - Thalhammer, Anja
T1  - Self-Assembly of Exendin-4-Derived Dual Peptide Agonists is Mediated by Acylation and Correlated to the Length of Conjugated Fatty Acyl Chains
JF  - Molecular pharmaceutics
N2  - Dual glucagon-like peptide-1/glucagon receptor agonists have emerged as promising candidates for the treatment of diabetes and obesity. Issues of degradation sensitivity and rapid renal clearance are addressed, for example, by the conjugation of peptides to fatty acid chains, promoting reversible albumin binding. We use combined dynamic and static light scattering to directly measure the self-assembly of a set of dual peptide agonists based on the exendin-4 structure with varying fatty acid chain lengths in terms of apparent molecular mass and hydrodynamic radius (R-S). We use NMR spectroscopy to gain an insight into the molecular architecture of the assembly. We investigate conformational changes of the monomeric subunits resulting from peptide self-assembly and assembly stability as a function of the fatty acid chain length using circular dichroism and fluorescence spectroscopy. Our results demonstrate that self-assembly of the exendin-4-derived dual agonist peptides is essentially driven by hydrophobic interactions involving the conjugated acyl chains. The fatty acid chain length affects assembly equilibria and the assembly stability, although the peptide subunits in the assembly retain a dynamic secondary structure. The assembly architecture is characterized by juxtaposition of the fatty acyl side chains and a hydrophobic cluster of the peptide moiety. This cluster experiences local conformational changes in the assembly compared to the monomeric unit leading to a reduction in solvent exposure. The N-terminal half of the peptide and a C-terminal loop are not in contact with neighboring peptide subunits in the assemblies. Altogether, our study contributes to a thorough understanding of the association characteristics and the tendency toward self-assembly in response to lipidation. This is important not only to achieve the desired bioavailability but also with respect to the physical stability of peptide solutions.
KW  - dual GLP-1/glucagon receptor agonist
KW  - self-assembly
KW  - light scattering
KW  - molecular architecture
KW  - lipidation
KW  - exendin-4
Y1  - 2020
U6  - https://doi.org/10.1021/acs.molpharmaceut.9b01195
SN  - 1543-8384
SN  - 1543-8392
VL  - 17
IS  - 3
SP  - 965
EP  - 978
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Wolff, Martin
A1  - Schüler, Anja
A1  - Gast, Klaus
A1  - Seckler, Robert
A1  - Evers, Andreas
A1  - Pfeiffer-Marek, Stefania
A1  - Kurz, Michael
A1  - Nagel, Norbert
A1  - Haack, Torsten
A1  - Wagner, Michael
A1  - Thalhammer, Anja
T1  - Self-Assembly of Exendin-4-Derived Dual Peptide Agonists is Mediated by Acylation and Correlated to the Length of Conjugated Fatty Acyl Chains
JF  - Molecular pharmaceutics
N2  - Dual glucagon-like peptide-1/glucagon receptor agonists have emerged as promising candidates for the treatment of diabetes and obesity. Issues of degradation sensitivity and rapid renal clearance are addressed, for example, by the conjugation of peptides to fatty acid chains, promoting reversible albumin binding. We use combined dynamic and static light scattering to directly measure the self-assembly of a set of dual peptide agonists based on the exendin-4 structure with varying fatty acid chain lengths in terms of apparent molecular mass and hydrodynamic radius (R-S). We use NMR spectroscopy to gain an insight into the molecular architecture of the assembly. We investigate conformational changes of the monomeric subunits resulting from peptide self-assembly and assembly stability as a function of the fatty acid chain length using circular dichroism and fluorescence spectroscopy. Our results demonstrate that self-assembly of the exendin-4-derived dual agonist peptides is essentially driven by hydrophobic interactions involving the conjugated acyl chains. The fatty acid chain length affects assembly equilibria and the assembly stability, although the peptide subunits in the assembly retain a dynamic secondary structure. The assembly architecture is characterized by juxtaposition of the fatty acyl side chains and a hydrophobic cluster of the peptide moiety. This cluster experiences local conformational changes in the assembly compared to the monomeric unit leading to a reduction in solvent exposure. The N-terminal half of the peptide and a C-terminal loop are not in contact with neighboring peptide subunits in the assemblies. Altogether, our study contributes to a thorough understanding of the association characteristics and the tendency toward self-assembly in response to lipidation. This is important not only to achieve the desired bioavailability but also with respect to the physical stability of peptide solutions.
KW  - dual GLP-1/glucagon receptor agonist
KW  - self-assembly
KW  - light scattering
KW  - molecular architecture
KW  - lipidation
KW  - exendin-4
Y1  - 2020
U6  - https://doi.org/10.1021/acs.molpharmaceut.9b01195
SN  - 1543-8384
VL  - 17
IS  - 3
SP  - 965
EP  - 978
PB  - American Chemical Society
CY  - Washington
ER  -