Physical Sciences and Mathematics Commons^™

A Chemoenzymatic Approach To The Synthesis Of Hemoglobin Oligomers, Johann Sigurjonsson

WWU Graduate School Collection

Polymerized hemoglobin (poly-Hb) molecules have been shown to have reduced toxicity compared to cell-free hemoglobins when transfused intravenously. Poly-Hbs are typically generated with non-specific crosslinking agents that yield a product that is polydisperse in molecular weight. We propose a chemoenzymatic approach to generate poly-Hb of defined molecular weight. The proposed method employs the site-specific ligation reaction of the sortase A enzyme from S. aureus. A Hb mutant previously developed in our lab has been “sortagged” – modified by adding either the sortase recognition sequence (LPXTG) to the C-terminus of the α-subunit or a tetraglycine motif (GGGG) to the N-terminus. …