Heparin-like activity via selective sulfation of bacteriophage Qβ
Author:
Griffin MeadMentor:
Andrew Udit, Assistant Professor of Chemistry, Occidental CollegeHeparins medical use is well established as a $4 billion industry per annum, but serious problems with quality control are inherent to heparins production. As a highly sulfated polysaccharide, heparin is heterogeneous in structure, an issue that has resulted in contaminated stocks, over-doses and deaths. Indeed, it has been estimated that only a third of heparin administered exhibits the desired physiologic effect due to this heterogeneity. As an alternative, we propose that a polyvalent sulfated bacteriophage (Qβ) can mimic heparin's physiologic activity while being safer due to the homogeneous nature of the sulfation process. The approach involves genetically modifying the bacteriophage coat proteins to express reactive moieties, which sulfated molecules can be coupled to using a specialized “click” chemistry. Organic synthetic chemistry has been used to synthesize mono- and tri-sulfated molecules. using a specially prepared solution of pyridine-sulfur trioxide and un-sulfated linker molecule in pyridine. Characterization of the sulfated linker was undertaken using high-pressure liquid chromatography (HPLC), which verifies the sulfated products. Currently, the thrust of research has been to optimize the copper-catalyzed azide-alkyne cyclo-addition “click” reaction used for coupling sulfated linker to the bacteriophage capsid.