Development of N-terminal targeting ligands for protein-material conjugation

Research within the Spicer group focuses on the synthesis of biomaterials for use in tissue engineering – the research I will present in this thesis focuses on the site-selective immobilization of extracellular matrix (ECM) signalling proteins to a synthetic tissue scaffold via the N-terminus. There are many different types of tissue scaffold that have been developed over the past few decades; synthetic tissue scaffolds are of particular interest due to their highly tuneable properties and biocompatibility. However, the main drawback of synthetic tissue scaffolds is their lack of cell adhesive motifs and bioactivity – this can be introduced in several ways. In this project we have focused on introducing bioactivity through immobilisation of ECM proteins to the scaffold via the N-terminus. The N-terminus of proteins has a very unique chemistry and can be targeted site-selectively without disruption to the protein’s structure or activity. Herein, we present the synthesis of poly (ethylene glycol) (PEG) tissue scaffolds functionalised with novel 2-pyridine carbaldehyde (2PCA) derivatives capable of specifically and reversibly binding to the N-terminus of proteins.