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Dimethyl adipimidate: a new antisickling agent.

B H Lubin, V Pena, W C Mentzer

    Proceedings of the National Academy of Sciences of the United States of America
    |January 1, 1975
    PubMed
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    Dimethyl adipimidate prevents red blood cells from sickling in vitro. This novel approach inhibits sickling and associated complications, offering a potential new avenue for sickle cell disease research.

    Area of Science:

    • Biochemistry
    • Hematology
    • Medical Chemistry

    Background:

    • Sickle cell disease is characterized by the sickling of red blood cells under deoxygenated conditions.
    • This sickling process leads to vaso-occlusion, pain, and organ damage.
    • Current treatments aim to manage symptoms or prevent sickling through various mechanisms.

    Purpose of the Study:

    • To investigate the antisickling potential of dimethyl adipimidate, a bifunctional crosslinking reagent.
    • To evaluate the effects of dimethyl adipimidate treatment on sickle erythrocytes.
    • To understand the underlying mechanisms of its antisickling properties.

    Main Methods:

    • Sickle erythrocytes were treated with dimethyl adipimidate in vitro.
    • Treated and untreated erythrocytes were subjected to deoxygenation.

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  • Measurements included potassium loss, viscosity changes, and hemoglobin analysis.
  • Oxygen affinity of hemoglobin was assessed.

    • Main Results:

    • Dimethyl adipimidate treatment inhibited sickling in deoxygenated sickle erythrocytes.
    • Treated cells showed no potassium loss or increased viscosity.
    • Hemoglobin oxygen affinity increased independently of 2,3-diphosphoglycerate levels.
    • Hemoglobin analysis revealed high-molecular-weight and positively charged components.

    Conclusions:

    • Dimethyl adipimidate demonstrates significant in vitro antisickling properties.
    • The reagent prevents key pathological changes associated with sickling.
    • Further research is needed to elucidate the precise role of chemical modification versus crosslinking in its efficacy.