Differential Binding Preference of Methylpheophorbide a and Its Diboronated Derivatives to Albumin and Low Density Lipoproteins
Galina V. Golovina,
Georgy N. Rychkov,
Valentina A. Ol’shevskaya,
Andrei V. Zaitsev,
Valery N. Kalinin,
Vladimir A. Kuzmin,
Alexander A. Shtil.
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
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