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Schwabenheim, Germany

Koch O.,Intervet Innovation GmbH | Koch O.,Molisa GmbH
Molecular Informatics | Year: 2012

Turns are essential for protein structure as they allow the polypeptide chain to fold backup on itself. They also occur within protein binding sites, at protein - protein interfaces and in small bioactive peptides, where they can play a crucial role for molecular recognition. Turn structures are an important class of protein secondary structure, although relatively little attention is paid to them with respect to helices and β-sheets. Protein structure prediction, functional analysis of proteins and peptides, and computer-aided drug design could all benefit from making use of accurately predicted turn structures from amino acid sequence. Here, recent advances of turn structure prediction and the underlying turn classification will be discussed together with their applications. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Wischke C.,Research Center Geesthacht GmbH | Wischke C.,Berlin Brandenburg Center for Regenerative Therapies | Neffe A.T.,Research Center Geesthacht GmbH | Steuer S.,Intervet Innovation GmbH | And 2 more authors.
European Journal of Pharmaceutical Sciences | Year: 2010

A family of oligo[(e{open}-caprolactone)-co-glycolide]dimethacrylate (oCG-DMA) derived networks of different glycolide contents as well as precursor molecular weights has been synthesized by crosslinking oCG-DMA, providing matrices of different hydrophilicity, network density, and morphology at body temperature. Such networks were loaded with a hydrophilic model drug, ethacridine lactate, either before crosslinking or afterwards by swelling in drug solution. Disadvantageous alterations of the shape-memory functionality and degradation characteristics were observed only in few loaded materials. Loading by swelling generally resulted in low payloads, which slightly increased for more hydrophilic polymer networks, and a substantial burst and fast subsequent release for all investigated materials. Loading before crosslinking gave almost no burst and higher subsequent release rates over longer periods of time. Overall, depending on the needs of a specific application, a material from this polymer family with the desired mechanical properties, shape-memory functionality, and degradation pattern can be selected and combined with drugs when considering that (i) loading by swelling is best suited for applications that require high initial doses and (ii) loading before crosslinking allows easy variation of payloads and low burst release for therapeutics that are non-sensitive to chemical alterations during crosslinking. © 2010 Elsevier B.V. Source

Desmolaize B.,University of Southern Denmark | Rose S.,University of Southern Denmark | Warrass R.,Intervet Innovation GmbH | Douthwaite S.,University of Southern Denmark
Molecular Microbiology | Year: 2011

Mannheimia haemolytica and Pasteurella multocida are aetiological agents commonly associated with respiratory tract infections in cattle. Recent isolates of these pathogens have been shown to be resistant to macrolides and other ribosome-targeting antibiotics. Direct analysis of the 23S rRNAs by mass spectrometry revealed that nucleotide A2058 is monomethylated, consistent with a Type I erm phenotype conferring macrolide-lincosamide resistance. The erm resistance determinant was identified by full genome sequencing of isolates. The sequence of this resistance determinant, now termed erm(42), has diverged greatly from all previously characterized erm genes, explaining why it has remained undetected in PCR screening surveys. The sequence of erm(42) is, however, completely conserved in six independent M. haemolytica and P. multocida isolates, suggesting relatively recent gene transfer between these species. Furthermore, the composition of neighbouring chromosomal sequences indicates that erm(42) was acquired from other members of the Pasteurellaceae. Expression of recombinant erm(42) in Escherichia coli demonstrated that the enzyme retains its properties as a monomethyltransferase without any dimethyltransferase activity. Erm(42) is a novel addition to the Erm family: it is phylogenetically distant from the other Erm family members and it is unique in being a bona fide monomethyltransferase that is disseminated between bacterial pathogens. © 2011 Blackwell Publishing Ltd. Source

Silley P.,MB Consult Ltd | Silley P.,University of Bradford | De Jong A.,Bayer AG | Simjee S.,Elanco Animal Health | Thomas V.,Intervet Innovation GmbH
International Journal of Antimicrobial Agents | Year: 2011

Antimicrobial surveillance systems in Denmark (DANMAP), The Netherlands (MARAN), Spain (VAV) and Sweden (SVARM) as well as the European Antimicrobial Susceptibility Surveillance in Animals (EASSA) were reviewed. Data have been considered for extended-spectrum cephalosporins, fluoroquinolones and macrolides against food-borne and commensal bacteria. The greatest challenge arises from the lack of agreement between programmes on what is meant by resistance through the use of different interpretive criteria. Indeed, it is shown here that the extent of the differences depends on the antibacterial compound being investigated, the methodology and the interpretive criteria used. This emphasises a need to agree a definition for resistance and for epidemiological cut-off values and to consider harmonising the antimicrobials used in surveillance. This analysis of the data highlights the usefulness of using both epidemiological cut-off values and clinical resistance breakpoints for the purpose of detection of decreased susceptibility and development of clinical resistance, respectively. It is concluded that harmonisation in resistance monitoring programmes is needed since there is potential for data to be appropriately used within risk analysis, providing the opportunity to implement appropriate risk management steps as a response to the public health issues arising from changes in antibiotic resistance in food-borne pathogens and commensal organisms. © 2011 Elsevier B.V. and the International Society of Chemotherapy. Source

Spehr V.,Intervet Innovation GmbH | Warrass R.,Intervet Innovation GmbH | Hocherl K.,University of Regensburg | Ilg T.,Intervet Innovation GmbH
Applied Biochemistry and Biotechnology | Year: 2011

(3′-5′)-Cyclic diguanylate (c-di-GMP) is a bacterial second messenger with immunomodulatory activities in mice suggesting potential applications as a vaccine adjuvant and as a therapeutic agent. Clinical studies in larger animals or humans will require larger doses that are difficult and expensive to generate by currently available chemical or enzymatic synthesis and purification methods. Here we report the production of c-di-GMP at the multi-gram scale from the economical precursors guanosine monophosphate (GMP) and adenosine triphosphate by a "one-pot" three enzyme cascade consisting of GMP kinase, nucleoside diphosphate kinase, and a mutated form of diguanylate cyclase engineered to lack product inhibition. The c-di-GMP was purified to apparent homogeneity by a combination of anion exchange chromatography and solvent precipitation and was characterized by reversed phase high performance liquid chormatography and mass spectrometry, nuclear magnetic resonance spectroscopy, and further compositional analyses. The immunomodulatory activity of the c-di-GMP preparation was confirmed by its potentiating effect on the lipopolysaccharide-induced interleukin 1β, tumor necrosis factor α, and interleukin 6 messenger RNA expression in J774A.1 mouse macrophages. © 2011 Springer Science+Business Media, LLC. Source

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