Funding tool: Basic research projects
Project-ID: LS13-012
Project start: 01. Februar 2015
Project end: will follow
Runtime: 36 months / finished
Funding amount: € 227.000,00

Brief summary:

Proteins and peptides are key mediators of all biological processes. Their unique chemical properties make them particularly attractive therapeutic agents. Peptides show high biological activity associated with low toxicity and high specificity. Peptides offer valuable chemical and biological diversity on which intellectual property is still widely available. Taking into account that far fewer academic and industrial laboratories are devoted to peptide drug development than to small molecules, it can be concluded that peptides are currently the most successful class of thera¬peutic agents. The market for synthetic therapeutic peptides will rise from €5.3 billion in 2003 to an estimated €11.5 billion in 2013. As a result the big pharmaceutical companies, traditionally focused on small molecules, are increasingly considering peptides in their pipelines.

In the present study we propose to further extend and technologically improve our existing peptide drug discovery platform. The major objective is the development of peptide lead candidates that modulate the activity of the epidermal growth factor receptor (EGFR) tyrosine kinase. EGFR signaling is critically involved in the development of most types of carcinomas. It drives cancer cell proliferation, survival, angiogenesis and metastasis. On the other hand, activation of the EGFR pathway in cell cultures might be beneficial for tissue engineering and regenerative medicine. Here we will combine rational design and high-throughput screening strategies to establish a powerful and interdisciplinary drug discovery platform for therapeutic peptide development. In the rational approach we will perform computer-assisted drug design (molecular modeling) to significantly minimize time and resource requirements for chemical synthesis and biologi¬cal testing. For combinatorial screening we will use our proprietary high-throughput yeast two-hybrid and phage display technologies. In the last years we have developed a large number of libraries (cDNA and peptide libraries, full-genome ORFeomes) that allow the rapid identification of first hit candidates. For the development of high affinity lead peptides we will perform experimental in vitro evolution that will be assisted by in silico molecular modeling. This field of study has matured over the last decade and it is now widely recognized that an integrated experi¬mental and theoretical approach is required for successful drug discovery. The project will fuel the development of sustainable and cost-effective technologies for biopharmaceutical drug discovery, therapeutic apheresis, toxin neutralization and tissue engineering. These research issues are addressed by many biotechnology companies residing in Lower Austria. Consequently the present study will be instrumental for the establishment of a local high-tech cluster in applied medical biotechnology and promote the launch of start-up companies in the near future.

Keywords:
peptide drugs, molecular modeling, in vitro evolution, targeted cancer therapies