Effect of sialic acid residues of human alpha 1-acid glycoprotein on stereoselectivity in basic drug-protein binding

Chirality
H ShionoT Nakagawa

Abstract

The function of sialic acid groups at the terminal of sugar chains of human alpha 1-acid glycoprotein (AGP) was investigated with respect to chiral discrimination between optical isomers of basic drugs, using high-performance capillary electrophoresis/frontal analysis (HPCE/FA), a novel analytical method developed for the determination of unbound drug concentration with ultramicrosample volume (100-200 nl). Native human AGP and desialylated AGP were used as test proteins, and propranolol (PRO) and verapamil (VER) were used as model drugs. The unbound concentration of (S)-VER was 1.31 times higher than that of (R)-VER in native AGP solution. This selectivity was not affected by desialylation. Further, enzymatic elimination of galactose residues, which neighbored sialic acid groups, did not change the binding of either isomer of VER. On the other hand, the unbound concentration of (R)-PRO was 1.27 times higher than that of (S)-PRO in native AGP solution. Desialylation caused the unbound concentration of (S)-PRO to rise to the same level of (R)-PRO, resulting in loss of enantioselectivity. Thus, it follows that sialic acid groups of AGP, as a whole, are not responsible for chiral recognition between enantiomers of VER but are invo...Continue Reading

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Citations

May 18, 2001·Journal of Biochemical and Biophysical Methods·Y Tanaka, S Terabe
Apr 10, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Akimasa ShibukawaIrving W Wainer
Jan 5, 2002·Journal of Pharmaceutical and Biomedical Analysis·Takanori OhnishiMicheal E El Kommos
Jan 30, 1999·Journal of Pharmaceutical and Biomedical Analysis·A ShibukawaT Nakagawa
Mar 7, 2000·Journal of Pharmaceutical and Biomedical Analysis·N A MohamedM E El Kommos
Sep 21, 2011·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Ahmed A OmranAhmed Shehata
Nov 18, 2003·British Journal of Clinical Pharmacology·T NakagawaK Miyazaki
Nov 19, 2008·Biomedical Chromatography : BMC·Laura Escuder-GilabertMaría José Medina-Hernández
May 30, 2006·Electrophoresis·Jesper Ostergaard, Niels H H Heegaard
Jul 2, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Koji NishiMasaki Otagiri
Jun 6, 2009·Chirality·Srinivas MaddiGerhard K E Scriba
Sep 25, 2015·Journal of Molecular Recognition : JMR·Vladimír KopeckýVladimír Baumruk

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