A study of the molecular interactions of hemoglobin with diverse classes of therapeutic agents

Abstract

Investigation of the interaction of hemoglobin (Hb) with therapeutic agents may be useful from three perspectives. First, there are a few therapeutic agents targeting precisely Hb. Second, the high concentration in the blood makes it a likely target for (often unwanted) side reactions of drugs targeting other systems in the body. Third, with its complex and well-studied reactivity, Hb offers itself as a useful model protein for understanding the interactions of therapeutic molecules with proteins via various mechanisms that include allosteric effects, coordination chemistry, metal- or aminoacid-based redox processes, and solution-based oxidative and nitrosative stress chain reactions. Presented here is a review of the molecular interactions described for hemoglobin with various therapeutic agents of organic, coordinative, or organometallic types. These interactions are typically studied by spectroscopy (fluorescence, UV–vis, circular dichroism, infrared, NMR), X-rays diffraction and molecular modeling (especially docking). Classes of therapeutic agents whose molecular interactions with Hb have been described include antioxidants (e.g., ascorbate, tocopherol, glutathione, carotenoids), anti-sickling agents, various organic chemotherapeutics, and metallodrugs.