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Glepaglutide, A Long-Acting GLP-2 Analog in Development for the Treatment of Short Bowel Syndrome
Zealand Pharma A/S
Discovery and Development of a New Class of Macrocyclic Peptide Antibiotics
Next generation peptide therapeutics
Overview of the expansions of peptides in:
Future opportunities for peptide therapeutics
The peptide discovery platform is based on an mRNA display technique that is able to identify a variety of high affinity binding peptides. They have typically macrocyclic scaffold and contain natural and non-natural amino acids. These peptides can support drug discovery projects in different manners and some examples will be shown. Further method developments and innovations to generate more impact of the platform will be also presented.
Aggregation of the alpha-Synuclein (aS) protein inside dopamine producing cells leads to PD by forming toxic Lewy bodies that interfere with normal brain function. We are utilising vast peptide libraries to identify those that both bind but most importantly are able to effectively block aS associated toxicity. Novelty lies in the fact that peptide selection is undertaken entirely inside living cells, with no assumptions made regarding mechanism of binding. Further novelty lies in the 45-54 region of aS which serves as a template for our library designs. This region is frequently mutated in early onset PD and is key to the pathogenic structure recently identified from CryoEM studies. Intracellular library screening and selection removes promiscuous peptides that bind to other proteins, as well as those that are unstable, insoluble, and degraded by enzymes. The most promising compounds have been characterised using a range of biophysical, structural, and cell-based experiments to i) increase understanding of how aggregation and toxicity are coupled, and ii) generate molecules for future use in PD diagnostics and prevention.
In parallel to activity optimisation at the target receptor(s), we consider physical & chemical peptide properties as primary optimisation parameter. For this purpose, orthogonal experimental methods and different in silico approaches are continuously implemented and applied in an iterative manner for the optimisation of functional, physical & chemical peptide properties, considering requirements of the final drug product.
An overview of progression of glepaglutide from lead optimisation to Phase III clinical studies.
This presentation focuses on the discovery of the outer-membrane targeting antibiotic (OMPTA) class applying PEM technology . OMPTAs target specifically Gram-negative bacteria by binding to lipopolysaccharide and outer-membrane proteins. Murepavadin (POL7080) is in phase III and the first member of this class . The discovery and development up to preclinical stage of a novel class of OMPTA with medium-spectrum activity against all Gram-negative priority 1/ESKAPE pathogens overcoming also colistin resistant strains will be described.
Panelists made up of a selection of speakers from the event
This evening workshop will focus on novel developments in the cost-efficient production of peptides. Through a series of presentations, the following areas will be addressed:
• Enzymatic peptide synthesis
• Silica based purification