| Autor: |
Möller C; Life Sciences Faculty, Albstadt-Sigmaringen University, 72488 Sigmaringen, Germany., Heinbockel L; Brandenburg Antiinfektiva GmbH, c/o Forschungszentrum Borstel, 23845 Borstel, Germany., Garidel P; Biophysikalische Chemie, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle (Saale), Germany., Gutsmann T; FG Biophysik, Leibniz Lungenzentrum, Forschungszentrum Borstel, 23845 Borstel, Germany., Mauss K; Brandenburg Antiinfektiva GmbH, c/o Forschungszentrum Borstel, 23845 Borstel, Germany.; Sylter Klinik, Dr.-Nicolas-Straße 3, 25980 Westerland (Sylt), Germany., Weindl G; Abteilung Pharmakologie und Toxikologie, Pharmazeutisches Institut, Universität Bonn, 53121 Bonn, Germany., Fukuoka S; Brandenburg Antiinfektiva GmbH, c/o Forschungszentrum Borstel, 23845 Borstel, Germany., Loser D; Life Sciences Faculty, Albstadt-Sigmaringen University, 72488 Sigmaringen, Germany.; NMI-TT GmbH, 72770 Reutlingen, Germany., Danker T; NMI-TT GmbH, 72770 Reutlingen, Germany., Brandenburg K; Brandenburg Antiinfektiva GmbH, c/o Forschungszentrum Borstel, 23845 Borstel, Germany. |
| Abstrakt: |
Aspidasept (Pep19-2.5) and its derivative Pep19-4LF ("Aspidasept II") are anti-infective and anti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections that could lead to systemic inflammation, as in the case of severe sepsis and septic shock, as well as application to non-systemic diseases in the case of skin and soft tissue infections (SSTI). In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B. Furthermore, the effects in mouse models of neurobiological behavior and the local lymph node according to OECD test guideline 429 were investigated, as well as a rat model of repeated dose toxicology according to ICH M3. The data provide conclusive information about potential toxic effects, thus specifying a therapeutic window for the application of the peptides. Therefore, these data allow us to define Aspidasept concentrations for their use in clinical studies as parenteral application. |
