Abstract
The tetrapyrrolic macrocycle and the functional groups at its periphery allow for a variety of modifications aimed at multifunctional therapeutic compounds. In particular, conjugation of boron polyhedra yields dual efficacy antitumor photo/ radiosensitizers. Structural optimization of these agents presumes the identification of macromolecules that bind and transport boronated tetrapyrroles. Using spectroscopic methods we demonstrated that methylpheophorbide a forms complexes with serum albumin and low density lipoproteins (LDL) whereas two diboronated derivatives, 13(2),17(3)-[di(o-carboran-1-yl)methoxycarbonyl]pheophorbide a and 13(2),17(3)-[di(1-carba-closo-dodecaboran-1-yl)methoxycarbonyl]pheophorbide a, were capable of binding to LDL but not to albumin. Molecular modeling showed a mode of interaction of methylpheophorbide a with the amino acid residues in the albumin’s hemin binding site. In contrast, for diboronated derivatives such interactions are sterically hindered by boron polyhedra, in line with experimentally determined lack of complex formation with albumin. These data strongly suggest that LDL might be the preferred carrier for polycarborane containing methylpheophorbide a derivatives.
Keywords: Methylpheophorbide a, Carborane, Albumin, Low density lipoproteins, Molecular modeling
Anti-Cancer Agents in Medicinal Chemistry
Title:Differential Binding Preference of Methylpheophorbide a and Its Diboronated Derivatives to Albumin and Low Density Lipoproteins
Volume: 13 Issue: 4
Author(s): Galina V. Golovina, Georgy N. Rychkov, Valentina A. Ol’shevskaya, Andrei V. Zaitsev, Valery N. Kalinin, Vladimir A. Kuzmin and Alexander A. Shtil
Affiliation:
Keywords: Methylpheophorbide a, Carborane, Albumin, Low density lipoproteins, Molecular modeling
Abstract: The tetrapyrrolic macrocycle and the functional groups at its periphery allow for a variety of modifications aimed at multifunctional therapeutic compounds. In particular, conjugation of boron polyhedra yields dual efficacy antitumor photo/ radiosensitizers. Structural optimization of these agents presumes the identification of macromolecules that bind and transport boronated tetrapyrroles. Using spectroscopic methods we demonstrated that methylpheophorbide a forms complexes with serum albumin and low density lipoproteins (LDL) whereas two diboronated derivatives, 13(2),17(3)-[di(o-carboran-1-yl)methoxycarbonyl]pheophorbide a and 13(2),17(3)-[di(1-carba-closo-dodecaboran-1-yl)methoxycarbonyl]pheophorbide a, were capable of binding to LDL but not to albumin. Molecular modeling showed a mode of interaction of methylpheophorbide a with the amino acid residues in the albumin’s hemin binding site. In contrast, for diboronated derivatives such interactions are sterically hindered by boron polyhedra, in line with experimentally determined lack of complex formation with albumin. These data strongly suggest that LDL might be the preferred carrier for polycarborane containing methylpheophorbide a derivatives.
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V. Golovina Galina, N. Rychkov Georgy, A. Ol’shevskaya Valentina, V. Zaitsev Andrei, N. Kalinin Valery, A. Kuzmin Vladimir and A. Shtil Alexander, Differential Binding Preference of Methylpheophorbide a and Its Diboronated Derivatives to Albumin and Low Density Lipoproteins, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (4) . https://dx.doi.org/10.2174/1871520611313040012
DOI https://dx.doi.org/10.2174/1871520611313040012 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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