Functional peptides by design

Proteins are nature's machines, built to function in many different ways. The ability to form so many functional molecules from the same few building blocks relies on the ability of these molecules to fold into specific structures. In this work, functional peptides are designed based on the information that has been gathered from nature concerning the relationships between sequence and structure. Chemists are not limited to naturally occurring amino acids, but may use any synthetically accessible residue imaginable. Herein, three novel amino acids are synthesized for facile incorporation into peptide sequences. These residues are designed to play a role in peptide folding through the formation of buried salt-bridges. They are small basic residues with varying hydrophobicity, and their ability to specify novel folds when incorporated into GCN4-p1 is demonstrated. Design is used to link intramolecular folding of another peptide to its function. MAX1 is designed to fold into a beta-hairpin structure upon the addition of distinct environmental stimuli. Once folded, this peptide self-assembles into a hydrogel material. Many applications can be envisioned for this hydrogel material, including its use as a tissue engineering scaffold. Cytocompatibility and antimicrobial activity studies demonstrate the ability of this hydrogel to support the selective proliferation of mammalian cells over certain bacterial strains. Thus, function has been successfully designed into a peptide.