[Seminar] "Racemic hydrogels from self-assembling mirror image peptides: Predictions from Pauling and Corey" by Dr. Joel P. Schneider, National Cancer Institute, NIH

Title
Racemic hydrogels from self-assembling mirror image peptides: Predictions from Pauling and Corey

Speaker
Dr. Joel P. Schneider, Chief of Chemical Biology Laboratory 
Head, Peptide Design and Materials Section
Center for Cancer Research Deputy Director, National Cancer Institute, NIH

Abstract
The beta-sheet is a ubiquitous protein fold whose propensity to aggregate has made it a valuable building block for the engineering of self-assembled materials. Lessons learned from studying the folding, misfolding and aggregation of sheet-rich proteins can be directly applied to the design of peptides that assemble into a vast array of sheet-containing nanostructures. Fibrils are privileged nanostructures capable of higher order assembly leading to the formation of networks that constitute the formation of macroscopic hydrogels. Gels prepared from self-assembling peptides are promising materials for medical applications, and using both L- and D-peptide isomers in a gel’s formulation provides an intuitive way to control the proteolytic degradation of an implanted material. In the course of developing gels for delivery applications, we discovered that a racemic mixture of the mirror-image b-hairpin peptides, named MAX1 and DMAX1, provides a fibrillar hydrogel that is four-times more rigid than gels formed by either peptide alone - a puzzling observation.  Transmission electron microscopy (TEM), small angle neutron scattering (SANS), solid state NMR, diffusing wave, infra-red, and fluorescence spectroscopies, and modeling was used to determine that enantiomeric peptides assembled into a structure predicted by Pauling and Corey in 1953, which provides the molecular basis for the increased mechanical rigidity of the racemic gel.  Molecular level understanding of the gel network allows the rational design of materials for specific applications, for example, multiphase transitioning gels that facilitate the suturing of ultrasmall blood vessels.