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Effect of sialic acid residues of human α 1 ‐acid glycoprotein on stereoselectivity in basic drug‐protein binding
Author(s) -
Shiono Hiromitsu,
Shibukawa Akimasa,
Kuroda Yukihiro,
Nakagawa Terumichi
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:3<291::aid-chir15>3.0.co;2-i
Subject(s) - chemistry , sialic acid , orosomucoid , enantiomer , affinity electrophoresis , glycoprotein , capillary electrophoresis , selectivity , biochemistry , chromatography , stereochemistry , enzyme , affinity chromatography , catalysis
The function of sialic acid groups at the terminal of sugar chains of human α 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 involved in enantioselectivity toward the isomers of PRO. Chirality 9:291–296, 1997. © 1997 Wiley‐Liss, Inc.