Project Details
Description
A novel approach is described for the detection of soluble aggregates of
deoxyhemoglobin S in dilute solution. It is based on the binding of
pteroylheptaglutamate (PteGlu7), which distinguishes between unpolymerized
and polymerized hemoglobin tetramers. The fraction of PteGlu7) bound will
be measured at constant PteGlu7 concentration (1x10 minus 6M) in the
presence of increasing hemoglobin concentrations in large excess. Under
these conditions the ratio of bound to free PteGlu7 is directly
proportional to the concentration of unpolymerized hemoglobin tetramers.
The measurements will be carried out by anaerobic ultrafiltration using 14C
labeled PteGlu7.
The investigations will be divided into: (1) Soluble aggregates as a
function of Hb concentration below the minimum geling concentration and (2)
Pregelation nuclei as a function of time during the delay period preceding
gelation.
The method will be used to explore the conditions influencing the formation
of pregelation aggregates and to characterize the intermolecular bonds
involved. This will include the effect of temperature, pH, ionic strength,
etc., as well as the use of chemically modified and mutant hemoglobins, the
effect of other rhemoglobins, which solubilize HbS, such as HbF and HbA2,
and, especially the influence of antisickling agents.
It is hoped that this study could lead to new strategies from a therapeutic
point of view, since it is possible that the sickling process could be
interrupted not only by preventing aggregation, but also by actually
stabilizing the soluble aggregates so as to prevent their further
polymerization into fibers.
Status | Finished |
---|---|
Effective start/end date | 9/30/85 → 1/1/90 |
Funding
- National Heart, Lung, and Blood Institute
ASJC Scopus Subject Areas
- Polymers and Plastics
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