Effect of the Sialylation State of α1-Acid Glycoprotein on Propranolol Binding

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

“…The sum of the unbound concentrations of PRO enantiomers decreased after desialylation, consistent with the previous results. 14,21 This suggests that both PRO enantiomers are bound in the single hydrophobic pocket on the AGP molecule 18 with the same affinity and that (S)-PRO can interact further with the sialic acid residue(s). As a result, (S)-PRO is bound to AGP more strongly than to (R)-PRO.…”

“…AGP was desialylated enzymatically, as outlined by Primozic and McNamara, 21 using an immobilized neuraminidase obtained from Clostridium perfringens. AGP (30 mg) was dissolved in 20 ml of phosphate buffer (pH 7.4, I = 0.17), and 3 units of enzyme was added.…”

“…Desialylation caused little change in the binding affinity of nicergoline, 17 dipyridamole, 18 and several quaternary ammonium compounds, such as thiazinamium, N-methylimipramine, N-methyldeptropine, and d-tubocurarine, 19 whereas the binding affinity of chlorpromazine was significantly decreased upon elimination of sialic acid residues. 18,20 The binding affinities of propranolol (PRO) 14,21 and several phenothiazine neuroleptics, except chlorpromazine, 20 decreased moderately. The binding affinity of many racemic drugs to AGP are known to be stereoselective.…”

.ALPHA.1-Acid Glycoprotein Suppresses Rat Acute Inflammatory Paw Edema through the Inhibition of Neutrophils Activation and Prostaglandin E2 Generation

“…Desialylation of AGP Human AGP was desialylated enzymatically, using methodology described by Primozic and McNamara, 24) using an immobilized neuraminidase obtained from Clostridium perfringens. Human AGP (40 mg) was dissolved in 5 ml of 67 mM phosphate buffer (pH 7.4) and 2 units of enzyme were added.…”

Effects of .ALPHA.1-Acid Glycoprotein on Erythrocyte Deformability and Membrane Stabilization.

“…Desialylation of AGP Human AGP was desialylated enzymatically, using methodology described by Primozic and McNamara, 14) using an immobilized neuraminidase obtained from Clostridium perfringens. Human AGP (40 mg) was dissolved in 5 ml of 67 mM phosphate buffer (pH 7.4) and 2 units of enzyme was added.…”