Peptide Materials from Self-Assembly and their Use in Therapy
Joel Schneider
Chief of Chemical Biology, Center for Cancer Research, NCI
Peptides have proven useful as building blocks for the construction of materials. It is now well-known that naturally derived or de novo designed peptides can assemble into a myriad of morphologies including membranes, nano- and microscopic spheres, tubes, ribbons, tapes, flowers and even teeth, to name a few. However, the most ubiquitous shape is most likely the fibril. The driving force for peptide-assembly into beta-sheet rich fibrils is formidable. Fibrils are privileged morphologies in that they are capable of higher-order assembly forming fibril networks that constitute the formation of hydrogel materials. The physical, mechanical and biological properties of peptide gels can be tuned through design at the molecular level to enable a wide range of therapeutic applications. Understanding the assembly mechanisms by which these materials are formed and the ultimate structures they form to molecular detail catalyze their development towards targeted biomedical applications. We designed a class of peptide hydrogels that allows for the direct encapsulation of therapeutics and their subsequent local delivery to tissue. Peptide assembly leading to gels can be triggered in the presence of small molecules, proteins, nucleic acids, cells, and nanoparticles resulting in their direct encapsulation. Resultant gels display shear-thin/recovery mechanical properties, allowing their direct application to targeted tissue by syringe or spray, where they deliver their payload locally. Through the design of over 200 sequences, we have developed a deep mechanistic and structural understanding of our materials. This has allowed the development of gels that facilitate a broad range of applications including microanastomosis, gels that limit tissue rejection after organ and vascularized composite allotransplantation, gel antibacterial coatings for medical implants, and gels as treatments for mesothelioma, a hard-to-treat cancer.
Joel Schneider received a Ph.D. in Organic Chemistry from Texas A&M developing turn mimetics to study b-sheet structure and then went on to the University of Pennsylvania as a postdoc to develop protein design principles to study ion channels and helical bundles. After which, he joined the faculty at the University of Delaware building a program in biomaterials. As Professor of Chemistry and Biochemistry at UD, he was recruited in 2010 to the National Cancer Institute, Center for Cancer Research (CCR) to serve as Chief and build their new Chemical Biology Laboratory. His group develops materials for use in the local delivery of therapeutics and as antibacterial agents. He is particularly interested in peptide-based hydrogels formed by self-assembly. He currently serves as Deputy Director of Basic Science, CCR, NCI and is past president of the American Peptide Society.