Enzyme Triggered Gelation of Arginine Containing Ionic-Peptides
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Enzyme Triggered Gelation of Arginine Containing Ionic-Peptides Jean-Baptiste Guilbaud1, Aline F. Miller2 and Alberto Saiani1,* 1
School of Materials, University of Manchester, Grosvenor Street, Manchester M1 7HS, UK. School of Chemical Engineering and Analytical Sciences and Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK. * corresponding author: E-mail: [email protected].
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ABSTRACT We have investigated the possibility of using the protease enzyme thermolysin to catalyse the synthesis and gelation of ionic-complementary peptides from non-gelling peptide precursors. In the described system, thermolysin was added at a fixed concentration (0.3 mg mL−1) to solutions (25 - 100 mg mL−1) of a short tetra-peptide FEFR. Initially, the protease partially hydrolysed the tetrapeptide into di-peptides in all samples. Subsequently, longer peptide sequences were found to form through reverse-hydrolysis and their stability was found to be dependent on their self-assembling properties. The sequences that self-assembled into antiparallel β-sheet rich fibres became the stable products for the reverse hydrolysis reaction, while the others formed were unstable and disappeared with increasing incubation time. Ultimately, the main product of the system was octa-peptide, which suggests that it represents the thermodynamically favoured product of this dynamic library. INTRODUCTION Molecular self-assembly has emerged as a powerful tool for the fabrication of molecular materials with a wide variety of properties. In recent years, considerable advances have been made in using simple, synthetic oligo-peptides as building blocks due to the propensity of such building block to self assemble into ordered supramolecular structure for the production of novel biomaterials. Of particular interest, being able to trigger the self assembly of these small molecules by an external stimulus such as enzyme, light, pH or ionic strength is attracting increasing attention as a route for the reversible fabrication of soft solid biomaterials due to their potential applications in drug delivery, bio-sensing or regenerative medicine. We have investigated the possibility of using the protease enzyme thermolysin to catalyse the synthesis of ionic complementary oligo-peptides via reverse hydrolysis, with subsequent trigger of their gelation. Such ionic oligo-peptides are known to readily self-assemble into β-sheet affording rich fibrillar hydrogels (1-4) and are gaining increasing popularity in the literature due to their potential biomaterials applications and for aiding the understanding of the general paradigms that govern molecular self-assembly. We successfully applied this approach starting from the tetra-peptide FEFK as the related octa-peptides FEFKFEFK and FEFEFKFK readily self-assemble into βsheet rich fibers to form self-supported hydrogels at low concentrations (10 and 15 mg ml−1 respectively).(5) Herein, this method was adapted using the tetra-peptide FEFR to fabricate
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