Association studies of aggregated aqueous lutein diphosphate with human serum albumin and alpha1-acid glycoprotein in vitro: evidence from circular dichroism and electronic absorption spectroscopy.

@article{citeulike:2449742, abstract = {Water-dispersible C40 carotenoid derivatives, with increased utility in mammalian therapeutic applications, include natural stereoisomer-based (3R,3'R,6'R)-lutein (beta,epsilon-carotene-3,3'-diol) derivatives. Esterification with inorganic phosphate and conversion to the sodium salt produced compounds (lutein diphosphate sodium salt; 'LdP') capable of forming red-orange aqueous suspensions after addition to USP-purified water. The aqueous dispersibility of this diphosphate salt reached 29 mg/mL without the addition of heat, detergents, co-solvents, or other additives, and was a potent direct scavenger of superoxide anion (by EPR spectroscopy) in an isolated human neutrophil assay. In the current study, preliminary evidence of the aqueous aggregation of this compound in EPR studies was confirmed using circular dichroism (CD) and electronic absorption (UV-vis) spectroscopy. Evidence for H-type ('card-pack') and J-type ('head-to-tail') self-assemblies was obtained. In vitro analysis of the potential binding interaction between LdP and human serum albumin (HSA) and alpha1-acid glycoprotein (AGP) revealed only non-specific binding with HSA (and none with AGP), contrasting with previous reports of direct interaction between astaxanthin-based soft drugs and the major plasma protein albumin. The rapid in vivo cleavage of this phosphodiester by promiscuous mammalian phosphatases may overcome the aqueous aggregation of the formulated compound. This difference in potential plasma protein interaction with prior reports reflects the subtle structural differences inherent in either the parent carotenoid scaffolds and/or the esterifying moieties.}, address = {Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, H-1525 Budapest, PO Box 17, Hungary.}, author = {Zsila, F. and Nadolski, G. and Lockwood, S. F. }, citeulike-article-id = {2449742}, doi = {http://dx.doi.org/10.1016/j.bmcl.2006.04.028}, issn = {0960-894X}, journal = {Bioorg Med Chem Lett}, month = {July}, number = {14}, pages = {3797--3801}, posted-at = {2008-03-01 00:51:58}, priority = {0}, title = {Association studies of aggregated aqueous lutein diphosphate with human serum albumin and alpha1-acid glycoprotein in vitro: evidence from circular dichroism and electronic absorption spectroscopy.}, url = {http://dx.doi.org/10.1016/j.bmcl.2006.04.028}, volume = {16}, year = {2006} }

TY - JOUR ID - citeulike:2449742 L3 - citeulike-article-id:2449742 TI - Association studies of aggregated aqueous lutein diphosphate with human serum albumin and alpha1-acid glycoprotein in vitro: evidence from circular dichroism and electronic absorption spectroscopy. JF - Bioorg Med Chem Lett VL - 16 IS - 14 SP - 3797 EP - 3801 AD - Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, H-1525 Budapest, PO Box 17, Hungary. SN - 0960-894X N2 - Water-dispersible C40 carotenoid derivatives, with increased utility in mammalian therapeutic applications, include natural stereoisomer-based (3R,3'R,6'R)-lutein (beta,epsilon-carotene-3,3'-diol) derivatives. Esterification with inorganic phosphate and conversion to the sodium salt produced compounds (lutein diphosphate sodium salt; 'LdP') capable of forming red-orange aqueous suspensions after addition to USP-purified water. The aqueous dispersibility of this diphosphate salt reached 29 mg/mL without the addition of heat, detergents, co-solvents, or other additives, and was a potent direct scavenger of superoxide anion (by EPR spectroscopy) in an isolated human neutrophil assay. In the current study, preliminary evidence of the aqueous aggregation of this compound in EPR studies was confirmed using circular dichroism (CD) and electronic absorption (UV-vis) spectroscopy. Evidence for H-type ('card-pack') and J-type ('head-to-tail') self-assemblies was obtained. In vitro analysis of the potential binding interaction between LdP and human serum albumin (HSA) and alpha1-acid glycoprotein (AGP) revealed only non-specific binding with HSA (and none with AGP), contrasting with previous reports of direct interaction between astaxanthin-based soft drugs and the major plasma protein albumin. The rapid in vivo cleavage of this phosphodiester by promiscuous mammalian phosphatases may overcome the aqueous aggregation of the formulated compound. This difference in potential plasma protein interaction with prior reports reflects the subtle structural differences inherent in either the parent carotenoid scaffolds and/or the esterifying moieties. AU - Zsila, F AU - Nadolski, G AU - Lockwood, SF PY - 2006/07/15/ UR - http://dx.doi.org/10.1016/j.bmcl.2006.04.028 ER -