Therapeutic Applications of Bioconjugates in Human Disease

Abstract

The unifying element tying together the therapeutics presented in this thesis is annexin A5. The protein, annexin 5 (ANXA5), is a membrane management protein that specifically binds to apoptotic cells. The natural ligand of ANXA5 displayed by apoptotic cells is phosphatidylserine. The aminophospholipid phosphatidylserine (Ptd-L-Ser) is a universal marker of mammalian cell stress. The expression of Ptd-L-Ser is triggered by a diverse range of cellular pathologies, most notably cellular trauma, oncogenesis, or infection. Annexin plays several critical roles in the pathogenicity of these disease states. Our previous work has demonstrated that ANXA5 derived therapeutics can be targeted to Ptd-L-Ser expression. In this thesis I build on this work, targeting several novel bioconjugates to Ptd-L-Ser expression.