Influence of elastase on alanine-rich peptide hydrogels

Abstract

The self-assembly of the alanine-rich amphiphilic peptides Lys(Ala)₆Lys (KA₆K) and Lys(Ala)₆Glu (KA₆E) with homotelechelic or heterotelechelic charged termini respectively has been investigated in aqueous solution. These peptides contain hexa-alanine sequences designed to serve as substrates for the enzyme elastase. Electrostatic repulsion of the lysine termini in KA₆K prevents self-assembly, whereas in contrast KA₆E is observed, through electron microscopy, to form tape-like fibrils, which based on X-ray scattering contain layers of thickness equal to the molecular length. The alanine residues enable efficient packing of the side-chains in a beta-sheet structure, as revealed by circular dichroism, FTIR and X-ray diffraction experiments. In buffer, KA₆E is able to form hydrogels at sufficiently high concentration. These were used as substrates for elastase, and enzyme-induced de-gelation was observed due to the disruption of the beta-sheet fibrillar network. We propose that hydrogels of the simple designed amphiphilic peptide KA₆E may serve as model substrates for elastase and this could ultimately lead to applications in biomedicine and regenerative medicine.