Association studies of aggregated aqueous lutein diphosphate with human serum albumin and α1-acid glycoprotein in vitro: Evidence from circular dichroism and electronic absorption spectroscopy

Ferenc Zsila, Geoff Nadolski, Samuel F. Lockwood

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Water-dispersible C40 carotenoid derivatives, with increased utility in mammalian therapeutic applications, include natural stereoisomer-based (3R,3′R,6′R)-lutein (β,ε-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 α1-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.

Original languageEnglish
Pages (from-to)3797-3801
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number14
DOIs
Publication statusPublished - Jul 15 2006

Keywords

  • AGP
  • Card-pack aggregation
  • HSA
  • Human serum albumin
  • Lutein
  • Lutein diphosphate sodium salt
  • Supramolecular assemblies
  • α-Acid glycoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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