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Related Experiment Videos

Eglin c, a pharmacologically active elastase inhibitor.

H P Schnebli, U Seemüller, H Fritz

    European Journal of Respiratory Diseases. Supplement
    |January 1, 1985
    PubMed
    Summary

    Eglin c, a leech-derived peptide inhibitor, effectively neutralizes human leukocyte elastase (HLE) and cathepsin G. This biotechnology product completely protected hamsters from emphysema induced by HLE, showing no toxicity.

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    Area of Science:

    • Biochemistry
    • Pharmacology
    • Biotechnology

    Background:

    • Eglin c is a potent elastase/cathepsin G inhibitor isolated from the medicinal leech Hirudo medicinalis.
    • The gene encoding Eglin c was synthesized, cloned, and expressed in E. coli, enabling biotechnological production.

    Purpose of the Study:

    • To characterize the biochemical and pharmacological properties of Eglin c.
    • To compare the inhibitory kinetics of Eglin c with naturally occurring proteinase inhibitors.
    • To evaluate the efficacy of Eglin c in a preclinical model of emphysema.

    Main Methods:

    • Determined the rate of complex formation between Eglin c and human leukocyte elastase (HLE) or human cathepsin G (H. Cat. G).
    • Compared association rate constants with alpha 1-proteinase inhibitor (alpha 1 PI) and alpha 2-macroglobulin (alpha 2M).

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  • Assessed Eglin c's protective effect against HLE-induced emphysema in a hamster model following intratracheal administration.

    • Main Results:

    • Eglin c exhibited association rate constants comparable to natural inhibitors like alpha 1 PI and alpha 2M.
    • Identical association rate constants were observed for both leech-extracted and biotechnologically produced Eglin c with HLE.
    • Equilibrium inhibition constants (Ki) for Eglin c/HLE and Eglin c/H. Cat. G interactions were in the order of 10(-10) M.
    • Intratracheal administration of Eglin c one hour prior to HLE insult completely prevented emphysema in hamsters.

    Conclusions:

    • Biotechnologically produced Eglin c demonstrates potent and comparable inhibitory activity to its naturally occurring counterpart.
    • Eglin c effectively prevents HLE-induced emphysema in a preclinical model.
    • Eglin c shows a favorable safety profile with no observed toxicity in the emphysema model.