The kinetic inhibition of the gelation of hemoglobin S is compared to the change in hemoglobin S soulbility, when the solubility is altered by carbon monoxide, pH, or urea. By means of a new technique, the delay time and the extent of gelation are measured on the same sample. They delay time, td, is found to be proportional to a high power (30-40) of the hemoglobin S solubility. Togehter with the previously reported concentration dependence, this result demonstrates that the rate is proportional to a high power of the supersaturation, S, defined as the ratio of the total hemoglobin S concentration to the equilibrium solubility. The results obey the supersaturation equation td-1 = gammaSn, where gamma is an empirical constant (about 10(-7) sec-1) and n is about 35. The supersaturation equation can successfully account for observations on the kinetics of cell sickling and is therefore used to estimate the increase in the delay time for sickling necessary to produce significant clinical benefit to patients with sickle cell disease.
Kinetics and mechanism of deoxyhemoglobin S gelation: a new approach to understanding sickle cell disease
The double nucleation model for sickle cell haemoglobin polymerization: full integration and comparison with experimental data
Modification of hemoglobin S with dimethyl adipimidate. Contribution of individual reacted subunits to changes in properties
Dependence on pH of formation and oxygen affinity of hemoglobin S fibers in the presence and absence of phosphates and polyphosphates
A multistage pathway for human prion protein aggregation in vitro: from multimeric seeds to β-oligomers and nonfibrillar structures
Proton longitudinal relaxation investigation of histidyl residues of normal human adult and sickle deoxyhemoglobin: evidence for the existence of pregelation aggregates in sickle deoxyhemoglobin solutions
Electron microscope study of the kinetics of the fiber-to-crystal transition of sickle cell hemoglobin
Light-scattering study of depolymerization kinetics of sickle hemoglobin polymers inside single erythrocytes
Sparing effect of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S at physiologic ligand saturations
Erythrocytes in sickle cell anemia are heterogeneous in their rheological and hemodynamic characteristics
Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes
Unlocked concanavalin A forms amyloid-like fibrils from coagulation of long-lived "crinkled" intermediates
ESR correlation times of 2,2,6,6-tetramethyl piperidone-N-oxyl (Tempone) in solutions of hemoglobin A and hemoglobin S
Amorphous Aggregation of Cytochrome c with Inherently Low Amyloidogenicity Is Characterized by the Metastability of Supersaturation and the Phase Diagram
Development of antisickling compounds that chemically modify hemoglobin S specifically within the 2,3-diphosphoglycerate binding site
Effects of ethanol and 3,4,-dihydron-2,2-dimethyl-2h-1-benzopyran-6-butyric acid on the solubility of sickle hemoglobin
Kinetics of sickle hemoglobin polymerization. III. Nucleation rates determined from stochastic fluctuations in polymerization progress curves
Polymerization of deoxyhemoglobin CHarlem (beta 6 Glu replaced by Val, beta 73 Asp replaced by Asn). The effect of beta 73 asparagine on the gelation and crystallization of hemoglobin
Chemical potential measurements of deoxyhemoglobin S polymerization. Determination of the phase diagram of an assembling protein
Gelation of sickle cell hemoglobin. IV. Phase transitions in hemoglobin S gels: separate measures of aggregation and solution--gel equilibrium
X-ray diffraction studies of 14-filament models of deoxygenated sickle cell hemoglobin fibers. Models based on electron micrograph reconstructions
Lawsone (2-OH-1,4-naphthoquinone) derived form the henna plant increases the oxygen affinity of sickle cell blood
Prostaglandin oligomeric derivatives inhibit in vitro formation of dehydrated cells from sickle red cells
A transcriptional signature of Alzheimer's disease is associated with a metastable subproteome at risk for aggregation
Quantitative assessment of the noncovalent inhibition of sickle hemoglobin gelation by phenyl derivatives and other known agents
Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers
Single cell microspectroscopy reveals that erythrocytes containing hemoglobin S retain a 'memory' of previous sickling cycles
Nitrite reductase activity of hemoglobin S (sickle) provides insight into contributions of heme redox potential versus ligand affinity
Hemoglobin S polymerization and sickle cell disease: A retrospective on the occasion of the 70th anniversary of Pauling's Science paper
Quantitative prediction of erythrocyte sickling for the development of advanced sickle cell therapies
Polymer structure and solubility of deoxyhemoglobin S in the presence of high concentrations of volume-excluding 70-kDa dextran. Effects of non-s hemoglobins and inhibitors.
Hb Shelby [beta 131(H9)Gln-->Lys] in association with Hb S [beta 6(A3)Glu-->Val]: characterization, stability, and effects on Hb S polymerization
Supersaturation-limited and Unlimited Phase Transitions Compete to Produce the Pathway Complexity in Amyloid Fibrillation.
Design, synthesis, and testing of potential antisickling agents. 9. Cyclic tetrapeptide homologs as mimics of the mutation site of hemoglobin S
Blood And Marrow Transplantation
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