Dynamics of Product Formation in Myeloperoxidose-H2O2 Chloride System

Research on the chemistry of myeloperoxidose (MP) is proposed, leading to design of an effector of dynamic drug delivery (automatically recurrent delivery of therapeutic activity in synchrony with the need to counteract a pathological process) in subsequent work. Such dynamic drug delivery, either of MP or of some species released in consequence of MP's activity, could maximize therapeutic effectiveness while reducing drug side effects. Simulations show prerequesite periodic reactions can be catalyzed by MP, an effector of periodicity. The system includes MP-H2O2-C1 and tyrosine reactions. It will be modulated by O2, CO2, and taurine.
A combined experimental and computational approach will lead to the goal of finding, analyzing and modeling domains of temporal periodicity in the concentration of compounds significantly contributing to the biochemistry of the MP chlorinating system in an in vitro environment approximating the leukocytric milieu. Regulation of the MP-H2O2-C1 system by the aforementioned species will be studied in the physiologically important range of pH (4.5 to 8.0) and temperature (298 to 318 K). Structure of intermediates and products will be analyzed. Collaborative theoretical modeling of MP structure-property relationships will be conducted. Required instrument adaptations and method development will be carried out. A stopped-flow spectrometer will be upgraded with modern electronics. Near infrared measurements will be developed to analyze species. NIR methods can later be used for in vito monitoring of dynamic drug delivery.
In subseqent work, periodic interaction will be elicited from cell cultured and subsequently tissues of mammals in steady contact with the drug delivery device developed as a consequence of this work.