Ponente
Descripción
Since decades peptide hormones like insulin, growth hormones, oxytocin etc. have been applied as biological drugs. Due to the tremendous progress in proteomics, peptidomics, mass spectrometry and bioscreening the number of new biologicals in clinical development has increased exponentially. Our research is focussed in the discovery and development new bioactive peptides from natural sources with major focus on antimicrobials (antivirals, antifungals and antibacterials) and anti-tumor peptides. For that purpose e.g. we are analyzing the “human peptidome”. In the human body from abundant precursor proteins specifically acting bioactive peptides are released by proteolysis resulting in the “human degradome“. From this human peptide pool we have discovered a plenty of new bioactive peptides. Their biological functions have been explored intensively and some of them have reached preclinical and clinical studies (e.g. EPI-X4 (Zirafi et al., 2015), VIRIP (Forssmann et al., 2010), SEVI (Münch et al., 2007)). The chemokine receptor-4 inhibitor (CXCR-4 inhibitor) EPI-X4 was undergoing a comprehensive structure activity relationship analysis (SAR) and its potency could be 1000-fold increased. Preclinical studies targeting the CXCR-4 are ongoing. The HIV-1 inhibitory peptide VIRIP was also optimized by SAR studies and a drug candidate (VIR-576) was successfully tested in clinical Phases I/II study. From the sperm-derived peptide SEVI which is a peptide that forms peptide fibrils and therefore enhances viral infectivity in vivo next generation peptide sequences were developed. A commercial available enhancer of retroviral gene transfer was developed: self‐assembling peptide nanofibrils (PNF) (Schütz et al., 2021).
Another interesting source for the discovery of new antimicrobial peptides (AMPs) are invertebrates which lack an adaptive immune system and therefore produce potent AMPs for their defense. From diverse Cuban snails we were able to identify potent antifungal, antibacterial and biofilm-inhibiting peptides.
Zirafi et al., Discovery and characterization of an endogenous CXCR4 antagonist. Cell Rep 2015 11:737-47.
Forssmann et al., Short-term monotherapy in HIV-infected patients with a virus entry inhibitor against the gp41 fusion peptide. Sci Transl Med 2010 2(63):63re3.
Münch et al., Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 2007 131:1059-71.
Schütz et al., 2021. Viral Transduction Enhancing Effect of EF‐C Peptide Nanofibrils Is Mediated by Cellular Protrusions Advanced Functional Materials (Wiley) 2021 31(40).
