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Band 3 peptides inhibit deoxy S polymerization: Viscosity studies
Author(s) -
Danish Elizabeth H.,
Lundgren David W.,
Harris John W.
Publication year - 1993
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830420120
Subject(s) - polymerization , chemistry , viscosity , medicine , pharmacology , materials science , organic chemistry , polymer , composite material
We have previously obtained evidence that N‐terminal band 3 peptides inhibited deoxyhemoglobin S (deoxy S) polymerization as determined by equilibrium solubility assays. An N:1‐15AA fragment binds to the 2,3‐diphosphoglycerate (2,3‐DPG) receptor locus of deoxy S with five to seven amino acids (AA) extending internally, while ten to eight AA remained external to deoxy S and inhibited polymerization by steric hindrance. A true mirror‐image peptide, corresponding to two N:1‐8AA + lysine (K) linked by coupler, binds to the 2,3‐DPG loci of two deoxy S molecules, tethering them together to form “binary complexes” incapable of entering the polymer chains. The reduction in the concentration of deoxy S available for extended chain formation decreased polymerization. We now report time:viscosity profiles of the sol‐gel transformation of purified solutions of deoxy S with and without peptides and studies of the gel solidity at equilibrium. Samples with peptides had longer lag times than controls of similar deoxy S concentrations. The mirror‐image peptide was a more effective inhibitor than the N:1‐15AA peptide. When the mirror‐image peptide was present in peptide:hemoglobin molar ratios of 0.25‐1:1, the increases in lag time were equivalent to decreasing the deoxy S concentrations by 15–25%, comparable to projected major therapeutic effects. Gel solidity, determined by yield temperature, was less in the sample with mirror‐image peptide compared to control. These results support the proposed mechanisms of inhibition of deoxy S polymerization by band 3 peptides. © 1993 Wiley‐Liss, Inc.