With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor Juan Del Valle from the University of South Florida. The project is an investigation of a new class of modified peptides that mimic protein structure. Proteins are the workhorses of the cell, and interactions between proteins govern many biological processes. The ability to modify these interactions with designed molecules (peptides) has been a long-standing challenge in chemistry. Professor Del Valle's work focuses on the mimicry of beta-sheets. This is a protein structure that is notoriously difficult to study due its tendency to clump together (aggregate). This research provides a toolkit for generating stable and aggregation-resistant mimics of the protein beta sheets. The project is also providing graduate and undergraduate students with rigorous training in laboratory research and scientific communication. The project is linked to the Tampa Preparatory School in an outreach effort providing internships to high school students.
This research project integrates molecular design, chemical synthesis, conformational analysis, and biological studies to fully characterize the properties of backbone-aminated peptides. The Del Valle laboratory recently established methods to prepare C-alpha-substituted N-amino peptides (NAPs) through conventional solid-phase peptide synthesis. This project develops optimal synthetic protocols toward cyclic, macrocyclic, and polyaminated NAP variants for bi-facial beta-strand mimicry. The motifs are evaluated in model systems for their specific effects on beta-sheet stability and self-association using a combination of nuclear magnetic resonance spectroscopy, circular dichroism, and X-ray diffraction. The discrete impact of NAP constraints on protease/serum stability and passive membrane permeability relative to control peptides are being examined.
