RUI: Protein Bioconjugation Strategies for Next Generation Silk Biomaterials

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Non-technical Abstract:Bombyx mori silkworms produce cocoons made of a fascinating protein called silk fibroin. In recent years, silk has become one of the most popular biomedical materials for applications ranging from drug delivery to creating artificial tissues. Successful development of the protein modification strategies described here will pave the way for researchers to design the next generation of innovative, functional silk-based biomaterials with enhanced performance and integration with biological systems. In the Department of Chemistry at Western Washington University, our core mission is to provide undergraduate students with significant, in-depth research opportunities. The proposed research program will involve a total of ~10-12 undergraduates and 2-3 master?s students over the three-year grant period. Recognizing that community colleges offer critical access to higher education for many underrepresented groups, this grant will provide one additional research stipend per summer for a local community college student. Overall, this work will give students a strong foundation in the skills required to be successful in STEM-related careers, will foster further collaborations between faculty both within and outside of WWU, and will continue to build relationships between WWU and local community colleges. Technical Abstract: Silk produced by the Bombyx mori silkworm has emerged as one of the most versatile biomaterials for applications ranging from engineered tissues, to drug delivery, to optical and electronic devices. Chemical modification of the silk protein provides an opportunity to further customize the interaction between silk and living systems, and endow silk with new functionality. Given the limitations in selectivity and functional group tolerance of previously employed bioconjugation methods, there is a need for complementary chemistries for silk modification, particularly bio-orthogonal reactions that occur under mild, aqueous conditions. To this end, the primary goal of this work is to develop new methods to chemically-modify the unusually high number of tyrosine residues in silk by employing 1) amino tyrosine modification strategies and 2) palladium-catalyzed cross-coupling reactions. While the methods developed here can be broadly applied, we will focus on silk derivatives that will be valuable for in vitro and in vivo imaging applications and targeted drug delivery. Overall, this work involves fundamental explorations of silk protein reactivity, furthers efforts to translate traditional organic reactions into aqueous environments, and ultimately will result in new protein bioconjugation methods that can be applied to silk and other tyrosine-containing proteins.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.