A potent new dipeptide inhibitor of cell sickling and haemoglobin S gelation
| Autor: | Arthur J. Hale, J. F. Pardon, Rosalind I. Cotter, Rosemary C. Cheetham, Ian M. Franklin, E. R. Huehns |
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| Rok vydání: | 1983 |
| Předmět: |
Chemical Phenomena
Hemoglobin Sickle Cell Biochemistry Cell membrane Mice chemistry.chemical_compound Biopolymers Oxygen Consumption Antisickling Agents In vivo medicine Animals Humans Centrifugation Incubation Erythrocyte Volume Binding Sites Dipeptide Erythrocyte Membrane Biological Transport Dipeptides Chemistry Membrane medicine.anatomical_structure Solubility chemistry Biophysics Hemoglobin Gels |
| Zdroj: | European Journal of Biochemistry. 136:209-214 |
| ISSN: | 1432-1033 0014-2956 |
| DOI: | 10.1111/j.1432-1033.1983.tb07728.x |
| Popis: | A dipeptide L-lysine-L-phenylalanine is shown to inhibit both cell sickling and the gelation of solutions of sickle-cell haemoglobin. The effect on deoxyhaemoglobin solutions and gels was followed by centrifugation; a progressive inhibition of gelation was observed up to 30 mM Lys-Phe. The haemoglobin concentration at the plateau (26 g/dl) suggests that an effect might be seen in vivo if suitable concentrations of Lys-Phe (about 20 mM) can be maintained in the blood stream. Additional studies of lag time before onset of gelation support this. Oxygen dissociation curves of sickle cells showed an effect of Lys-Phe only after incubation for 3 h before measurement, the P50 decreasing from 51 mmHg (6.8 MPa) to 41 mmHg (5.5 MPa) for cells depleted of 2,3-bisphosphoglycerate. The effect of Lys-Phe on intact sickle cells was more rapid. A marked increase in the number of unsickled cells in the presence of Lys-Phe was observed after only 15 min incubation. This result, together with measurements of uptake both into the cell and onto the cell membrane shows that the compound produces a membrane-mediated antisickling effect in addition to the effect on haemoglobin in solution within the cell. The membrane effect is not due to a change in cell volume. The properties of this dipeptide may be of value in the treatment of impending and early sickle crisis. |
| Databáze: | OpenAIRE |
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