Precise, autocatalytic chemistry on proteins and peptides

Chemical and molecular biology skills joined to develop a system for testing if acylation can be performed at specific sites and if introduced modifications improves stability. Thus, providing proteins and peptides with enhanced pharmaceutical properties.

About the project

This project will investigate site-specific acylation of proteins and peptides, with a focus on developing improved therapeutics. Different functional moieties will be attached to proteins or peptides via optimized amino acid sequences (Lys-His tag) placed in flexible terminals or internal loop regions to achieve or enhance serum-stability and/or cell-toxicity. 

Project information

Primary investigator (PI)

Project period

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The central focus will be on the protein alpha-1 antitrypsin (A1AT), belonging to the serpin superfamily and the antibody Rituximab. Proteins comprising human-like glycosylation patterns will be achieved by production in glyco-engineered Saccharomyces cerevisiae and Chinese Hamster Ovary cells. Furthermore, peptide inhibitors of the essential fungal protein Pma1 will be modified to enhance serum-stability and cell-permeability. Lys-His tags will be optimized to achieve optimal acylation efficiency, and the activity and stability of acylated protein/peptide conjugates will be assessed through binding studies, enzyme assays, and cell-toxicity assays.

Researchers

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