Sickle Cyanate

Val 1-NAl, Lys 82-EF6, and His 143-H21) and deoxy Hb-S does not produce configuration changes which influence the aggregation of the molecules (B35). Moreover, cyanate (HN=C=0) which carbamylates amino terminal residues of proteins (R—NH—CO—NH2) is an effective inhibitor of sickling of erythrocytes in vitro and of gelling of concentrated solutions of deoxyhemoglobin S (C9). Addition of some specific hemoglobin variants, Hb-O-Arab or 02 2 (M16) and Hb-Korle Bu... 

The reaction of proteins with cyanate has been exploited in the development of a method for the quantitative determination of NH2-terminal residues (Stark 1967a), as well as in a variety of interesting structure-function studies exemplified by those of Smyth (1967) on oxytocin, and Cerami and Manning (1971), as well as Lee and Manning (1973), on sickle cell hemoglobin. Whereas cyanate reacts with a-NH2, -NH2, thiol, imidazole, and phenolic OH groups of proteins, only the amino group derivatives are stable at alkaline pH. 

A very simple compound, cyanate, was found to inhibit coagulation when used for treatment of blood from sickle cell anemia patients.78 It decreased the levels of Factor V and X activity (19 and 367. respectively), inhibited Factors VII, IX, and XI (63-75%), and inhibited thrombin 807.. 

In the same editorial, it is mentioned that some 80% of the diet for people in regions of tropical Africa comprises sorghum, millet, cassava, and yams. These foods contain nitrilosides that can react to form thiocyanate, which in turn may be oxidized to cyanate. And cyanate is a known inhibitor of sickle cell anemia. Whereas sickle cell anemia occurs in ronghly 1 ont of 50 genetically disposed persons in the United States, the rate in tropical Africa is less than 1 in a 1000. The inference is that the nitriloside-containing diet is connteractive. An aside is that people who have sickle cell anemia (the natives of Africa) do not contract malaria. 

Knowledge of the molecular alteration in sickle cell anemia has contributed to an understanding of the pathogenesis of the disease and has also generated some hope for therapy. Two compounds have been used in the treatment of sickle cell anemia urea and cyanate. 

When cyanate is administered to animals, most of the radioactivity is accounted for by carbamylation of NH2-terminal residues of hemoglobin. No detectable carbamylation of lysine or cystine residues is observed. The exact mechanism by which cyanate protects against sickling is not known. Because cyanate... 

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