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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Jan;80(2):324–328. doi: 10.1073/pnas.80.2.324

Physiological and x-ray studies of potential antisickling agents.

D J Abraham, M F Perutz, S E Phillips
PMCID: PMC393369  PMID: 6572894

Abstract

Several aromatic compounds have been found to inhibit the gelling of sickle cell hemoglobin. We have tried to correlate the antigelling activity of such compounds with the stereo-chemistry of their binding sites in the hemoglobin molecule. This approach led to the discovery that two known antilipoproteinemia drugs, clofibrate and gemfibrozil, have antigelling activity. X-ray analysis showed that three pairs of molecules of clofibric acid, the active metabolite of clofibrate, bound to the walls of the internal cavity of deoxyhemoglobin A; only one pair bound to a quite different site, between helices A, E, and H of the alpha chains of carbon monoxide hemoglobin A. Unlike other antigelling agents, clofibric acid and related compounds decrease rather than increase the oxygen affinity of hemoglobin.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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