Alpha1- acid glycoprotein (AGP) is an acute phase glycoprotein consists of 183 amino acid and 5 sugar chains, which mainly binds basic drugs in the general circulation. We have proposed, so far, that AGP has binding regions for basic drugs, acidic drugs and steroid hormones, which overlap with each other. Unfortunately, three dimensional X-ray structure of AGP is unknown and despite the vast literature data on small molecule-AGP interactions, the topology of binding sites and the binding mechanism are not well understood. Identification of drug binding site on AGP molecule seems to be useful for the prediction of drug-drug interaction.
　On the other hand, the mechanism of elimination of AGP from the blood and the site of accumulation of AGP in the body remain unknown. Elucidation of this information is very important for the understanding of pharmacokinetics of the drug bound to AGP and physiological function of AGP.

In our laboratory, the following research topics are currently underway:

　1. Mapping of drug binding site on AGP molecule using photoaffinity labeling techniques.

　2. Evaluation of structural and functional characteristics of AGP interacting with biomembrane. 　

　3. Elucidation of oligosaccharide chain and specific receptor involved in elimination of AGP from blood. 　

　4. Elucidation of protection mechanism by AGP in acute inflammation disease.

Reference（２０００〜）

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Nishi K, Komine Y, Fukunaga N, Maruyama T, Suenaga A, Otagiri M. Related Articles, Links Involvement of disulfide bonds and histidine 172 in a unique beta-sheet to alpha-helix transition of alpha 1-acid glycoprotein at the biomembrane interface. Proteins. 63:611-620 (2006)

Nishi K, Komine Y, Sakai N, Maruyama T, Otagiri M. Cooperative effect of hydrophobic and electrostatic forces on alcohol-induced alpha-helix formation of alpha(1)-acid glycoprotein. FEBS Lett. 579:3596-3600 (2005).

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Nishi K, Fukunaga N, Otagiri M. Construction of expression system for human alpha1-acid glycoprotein in Pichia pastoris and evaluationof its drub binding properties. Drug. Metab. Dispos. 32:1069-1074 (2004).

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Matsumoto K, Nishi K, Tokutomi Y, Irie T, Suenaga A, Otagiri M. Effects of alpha1-acid glycoprotein on erythrocyte deformability and membrane stabilization. Biol. Pharm. Bull. 26:123-126 (2003).

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