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  • Journal
    Digital Access
    Provider
    Version
    LWW
    v. 1-, 2007-
    PubMed Central
    v. v. 6-, 2012-
    Karger
    v. 1-14, 2007-20.
  • Article
    Martodam RR, Twumasi DY, Liener IE, Powers JC, Nishino N, Krejcarek G.
    Proc Natl Acad Sci U S A. 1979 May;76(5):2128-32.
    Methods are described for the covalent attachment of succinoyl-Ala-Ala-Pro-ValCH2Cl, an active site-directed inhibitor of human leukocyte elastase (EC 3.4.21.11), to microspheres of human albumin. The insertion of side arms of various lengths revealed that maximum inhibition of this enzyme was obtained when the spacer arm was at least 24.3 A in length. Approximately 30 molecules of the inhibitor could be attached to each molecule of albumin. Such derivatized microspheres were capable of inhibiting approximately one mole of elastase per mole of albumin, which is comparable to the inhibitory activity of alpha 1-antitrypsin. Experiments in vivo in which rats were injected intravenously with radiolabeled microspheres to which the inhibitor had been attached showed a rapid and exclusive uptake by the lungs. About 40--50% of the injected microspheres subsequently remained in the lungs with a half-life of approximately 17 days. These derivatized microspheres thus appear to offer promise as a therapeutic agent for emphysema.
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