Measuring Thermodynamics of Peptides with Complementary Stereochemistry to Guide the Design of New Materials for Medicine

As the complexity of biological systems and tunability of synthetic materials are further understood, opportunities for engineers to design synthetic materials that interact with the natural world seamlessly are brought to light. For this project, synthetic materials will contain synthetic polymers and complementary peptides. Peptides – molecules consisting of two or more amino acids – with complementary stereochemistry exhibit opposite twists because of their contrasting three-dimensional configurations. Complementary peptides have been demonstrated to display strong unique binding properties when compared to peptides with uniform stereochemistry. This project involves the use of Isothermal Titration Calorimetry (ITC), a technique that determines thermodynamic parameters associated with interactions, to derive a relationship between peptide structure and binding strength between peptides with opposite stereochemistry. Having successfully learned this technique and optimized experimental conditions with several model systems, we are in the process of conducting a larger investigation exploring the effects of peptide length, electrostatic forces, order of peptide addition, and length of polymer attachments on peptide binding strength. Such knowledge could ultimately be used to design peptides to sequester toxic dipeptide repeats in Amyotrophic Lateral Sclerosis (ALS) patients, construct shape memory biomaterials, trigger wound healing and injury repair, and deliver drugs