Revisiting Chiral Recognition Mechanism on Chicken Alpha 1-Acid Glycoprotein: Location of Chiral Binding Sites and Insight into Chiral Binding Mechanism

被引:4
|
作者
Haginaka, Jun [1 ]
Yamashita, Taku [2 ]
Tsujino, Hirofumi [3 ]
Arisawa, Mitsuhiro [3 ]
机构
[1] Mukogawa Womens Univ, Inst Biosci, 11-68 Koshien Kyuban Cho, Nishinomiya, Hyogo 6638179, Japan
[2] Mukogawa Womens Univ, Sch Pharm & Pharmaceut Sci, 11-68 Koshien Kyuban Cho, Nishinomiya, Hyogo 6638179, Japan
[3] Osaka Univ, Grad Sch Pharmaceut Sci, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan
关键词
protein-based chiral stationary phase; alpha 1-acid glycoprotein; chiral recognition mechanism; molecular docking; LIQUID-CHROMATOGRAPHIC RESOLUTION; HUMAN ALPHA(1)-ACID GLYCOPROTEIN; INDUCED CIRCULAR-DICHROISM; DRUG-BINDING; STATIONARY-PHASE; SERUM-ALBUMIN; PROTEIN; SEPARATION; ENANTIOMERS; DOCKING;
D O I
10.3390/separations8060073
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Chiral stationary phases based on chicken alpha 1-acid glycoprotein (cAGP) have been used for enantioseparations of various compounds. However, the chiral binding sites and mechanism have not been clarified yet. Based on chromatographic properties of native and W26-modified cAGP columns and docking simulations of studied compounds into the generated model structure of cAGP, the chiral binding sites were located on cAGP and the chiral binding mechanism was discussed. On cAGP, there existed a binding cavity lined with H25, W26, Y47, R128, T129, D161 and E168, which contribute electrostatic or hydrogen bonding interactions. Benzoin and chlorpheniramine enantiomers interacted with cAGP at almost the same sites a little away from W26, while propranolol enantiomers docked, slightly shifting toward H25 and W26. Furthermore, in addition to hydrophobic interactions, ionic interactions between amino groups of chlorpheniramine enantiomers and a carboxyl group of D161 or E168 played an important role in the chiral recognition, while hydrophobic interactions and hydrogen bonding interactions worked for the chiral recognition of benzoin and propranolol enantiomers.
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页数:10
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