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  • Title: Polylysine conjugates of Bowman-Birk protease inhibitor as targeted anti-carcinogenic agents.
    Author: Persiani S, Yeung A, Shen WC, Kennedy AR.
    Journal: Carcinogenesis; 1991 Jun; 12(6):1149-52. PubMed ID: 2044199.
    Abstract:
    Bowman-Birk protease inhibitor (BBI), an 8000 mol. wt polypeptide with anti-carcinogenic activity, was coupled to poly(D-lysine) (BBI-SS-PDL) and poly(L-glutamate) (BBI-SS-PLG) with a disulfide-cross-linking agent, N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). In vitro transformation assays showed that BBI-SS-PDL, but not BBI-SS-PLG, retained the full anticarcinogenic activity of BBI. When administered i.v. to Balb/c mice, a selective localization in the lungs was found with BBI-SS-PDL but not with BBI or BBI-SS-PLG. At 30 min, 3 h and 24 h after the injection of BBI-SS-PDL, the amounts of BBI in the lungs were 118%, 74% and 19% of the injected dose/g of tissue respectively. At the same time points, the amount of radioactivity in the lungs of mice injected with BBI was 5%, 3% and 1% of the injected dose/g of tissue respectively. Therefore, higher amounts of BBI could be targeted to the lungs by injecting BBI as a PDL conjugate. BBI-SS-PDL was also retained in the lungs for a longer period of time than free BBI. In previous studies, BBI has been shown to suppress lung carcinogenesis. The results presented here suggest that BBI-SS-PDL could be more effective than BBI as an anti-carcinogenic agent for the lung.
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