Presentation description

Biotin, also known as D-biotin or (+)-biotin, is a water-soluble B vitamin notable for its strong and selective interactions in biological systems. Its femtomolar binding affinity to the protein streptavidin has enabled widespread use of biotin as a molecular handle in streptavidin-based purification and labeling strategies. Streptavidin's exceptional specificity and high affinity for D-biotin highlight many of these techniques. This project focuses on the synthesis of L-biotin, the enantiomer of naturally occurring D-biotin. Previous studies suggest that L-biotin may exhibit enhanced binding affinity to engineered streptavidin variants compared to natural D-Biotin, while remaining orthogonal to endogenous D-biotin, making it a promising tool in biorthogonal chemistry. The process of biological synthesis of peptides, as well as the biochemical applications of creating mirror images of naturally occurring organic molecules, allows for discovery of new possibilities with the potential to open novel pathways in therapeutics and biochemistry. The synthesis will be achieved through established organic synthesis routes, highlighting the complexity and precision required for enantiomeric total synthesis. Following synthesis, in collaboration with the Kay-Laboratory (U of U Biochemistry,) binding assays will be conducted with both natural and engineered streptavidin to evaluate the specificity and potential applications of L-biotin. This work may open new avenues for therapeutic development and selective biomolecular labeling.