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Binding of a spin‐labeled phenylalanine analog to sickle hemoglobin: EPR and NMR studies
Author(s) -
Lu Hwei-Zu,
Currie Bruce L.,
Johnson Michael E.
Publication year - 1984
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(84)81059-5
Subject(s) - hemoglobin , phenylalanine , chemistry , electron paramagnetic resonance , nuclear magnetic resonance , crystallography , stereochemistry , biochemistry , amino acid , physics
We have synthesized a spin‐label analog of phenylalanine as a competitive inhibitor probe of the sickle hemoglobin aggregation process. Sickle hemoglobin gelation measurements indicate that the spin‐label phenylalanine analog is a potent inhibitor of deoxy sickle hemoglobin aggregation. We have also used spin label EPR and high‐resolution proton NMR to study the interaction of the phenylalanine analog with hemoglobin, and find that the kinetic off‐rate is comparable to, or slower than the hemoglobin rotational rate (i.e., ⪸ 10 8 s −1 ), and that at least one, and perhaps two significant localized interaction region(s) exist within a few angstroms of the β chain N‐ and C‐termini. Correlation with other known structural information suggests that the observed interaction sites may be relevant to the mechanism for inhibition of sickle hemoglobin aggregation.