Hemoglobin, interaction with small molecule

The major problem with designing a small molecule to treat sickle cell anemia is not so much an issue of specificity, but arises from the treatment of a chronic disease. The potential cumulative toxicity from the amount of drug needed to interact with approximately two pounds of hemoglobin S over a homozygous patient s lifetime is the major concern (22) (for a review, see Vol. 3, Chapter 10. Sickle Cell Anemia, by Alan Schecter et al). 

Redox proteins are relatively small molecules. In biological systems they are membrane associated, mobile (soluble) or associated with other proteins. Their molecular structure ensures specific interactions with other proteins or enzymes. In a simplified way this situation is mimicked when electrodes are chemically modified to substitute one of the reaction partners of biological redox pairs. The major classes of soluble redox active proteins are heme proteins, ferredoxins, flavoproteins and copper proteins (Table 2.1). In most cases they do not catalyze specific chemical reactions themselves, but function as biological (natural) electron carriers to or between enzymes catalyzing specific transformations. Also some proteins which are naturally not involved in redox processes but carry redox active sites (e.g., hemoglobin and myoglobin) show reversible electron exchange at proper functionalized electrodes. 

It should be realized that the ability to bind oxygen reversibly is a unique property found in nature only in iron-porphyrin proteins, iron proteins, and copper proteins. However, other small molecules such as CO, CO2, or CN" can also interact with these metalloproteins. In fact, CO binds to hemoglobin even more avidly than oxygen, producing a cellular oxygen deficiency, which is sometimes identified as carbon monoxide poisoning. ... 

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