Characterization and Application of Heme Protein-Based Nitric Oxide Donors from Bloodsucking Insects

• Applicant: Dr. Markus Knipp
• Subject Area: Biochemistry
• Term: from 2008 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 81589345

NO is a central signaling molecule in cardiovascular regulation. Despite great effort to invent synthetic NO donating molecules for the treatment of the numerous NO related diseases very few have been introduced in the clinic. In contrast, the saliva of two blood-sucking insects contains a class of NO donor proteins termed nitrophorins (NPs) that transport NO coordinated to their ferriheme cofactor. The saliva is injected into a victim’s blood stream to apply NO during feeding which causes vasodilation and inhibition of blood coagulation. Because of the successful application of NPs in nature, these protein-based NO donors are of exceptional pharmaceutical potential. This study aims at the detailed understanding of the NO storage capabilities and the triggering mechanism of NO release at a defined target site, i.e, a specific cell or tissue. For the latter, native and artificial triggers will be considered. Another important aspect of this study is the detailed understanding of the interaction and reactivity of NPs with blood components. The results of this study will reveal guidelines for a successful biomimetic design of specific NO-donor therapeutics for cardiovascular or other diseases, e.g., cancer. Furthermore, the study is the first step for the invention of NPs and chemical or molecular biological variants as protein-based NO-delivery systems with pharmacotherapeutic potential. (Keywords: cancer therapy, cardiovascular pharmacology, heme proteins, cell membrane diffusion, nitric oxide, nitrite, nitrophorins, nitrosyl complex, NO release)

• DFG Programme: Research Grants