Bis (N maleimidomethyl) ether: an antisickling reagent

S. J. Zak, G. R. Geller, B. Finkel, D. P. Tukey, M. K. McCormack, W. Krivit

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The interaction of bis (N maleimidomethyl) ether with oxyhemoglobin results in covalent linkages of both maleimide groups, converting them to succinyl derivatives of β 93 Cys and β 97 His at their sulfhydryl and imidazolyl side chains, respectively. The resultant hemoglobin is stable, and reveals a left shifted oxyhemoglobin equilibrium curve in which cooperativity is abolished. This reagent readily traverses the red cell membrane and prevents the sickling reaction upon deoxygenation. It appears to affect none of the activities of the red cell enzymes adversely, nor does it appear to affect the red cell membrane. Since there are several defined effects on the stereochemical status of the molecule conferred by interaction with bis (N maleimidomethyl) ether, the precise mechanism of the antisickling effect remains to be elucidated. A more subtle perturberant will be required to specify a precise antisickling effect. By use of bis (N maleimidomethyl) ether a precise locus on the β chain human hemoglobin S can be perturbed to produce the desired effect.

Original languageEnglish (US)
Pages (from-to)4153-4156
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - 1975
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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