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Metallocorroles for Attenuation of Atherosclerosis

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Abstract

Biodistribution of medications is a major factor dictating therapy efficacy, as demonstrated by many very excellent in vitro performing drugs displaying limited in vivo efficiency. Every therapeutic first encounters the serum components, which may bind it and serve as carriers for its delivery within the body. Accordingly, serum distribution of potential drugs is a main issue of their activity, and the first step disclosed in this research. Earlier studies have focused on the interaction of the bis-sulfonated corrole metal complexes with isolated serum proteins. These investigations revealed very strong binding of the corroles to the most abundant serum proteins transferrin and albumin (with dissociation constants of 10−7–10−9 and >10−9 M, respectively). Examinations of corrole interaction with isolated lipoproteins revealed high affinity binding in this case as well, and a binding stoichiometry of about 40 corrole molecules to isolated LDL and 10 to isolated HDL. Together these results underline the need to directly explore the distribution of the corroles in whole serum, as strong binding may be outcompeted by stronger binding, and because the equilibrium between the various serum components depends also on their relative concentrations.

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Notes

  1. 1.

    HDL contains albumin (even when isolated), as may be seen from the SDS-PAGE experiments.

  2. 2.

    The effective concentration of 1-Fe for the SIN-1 induced oxidation was tenfold higher than in the copper ions induced oxidation. However, lipoprotein concentration was also increased tenfold in the former relative to the latter. See experimental section for further details.

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  1. Technion—Israel Institute of Technology, Haifa, Israel

    Dr. Adi Haber

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Haber, A. (2012). Discussion. In: Metallocorroles for Attenuation of Atherosclerosis. Springer Theses. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30328-9_4

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