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Research ArticleArticle

Subdomain IIIA of Dog Albumin Contains a Binding Site Similar to Site II of Human Albumin

Ken-ichi Kaneko, Hikaru Fukuda, Victor Tuan Giam Chuang, Keishi Yamasaki, Kohichi Kawahara, Hitoshi Nakayama, Ayaka Suenaga, Toru Maruyama and Masaki Otagiri
Drug Metabolism and Disposition January 2008, 36 (1) 81-86; DOI: https://doi.org/10.1124/dmd.107.016873
Ken-ichi Kaneko
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Hikaru Fukuda
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Victor Tuan Giam Chuang
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Keishi Yamasaki
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Kohichi Kawahara
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Hitoshi Nakayama
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Ayaka Suenaga
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Toru Maruyama
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Masaki Otagiri
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Abstract

Dog albumin contains a specific drug-binding site that binds most of the site II ligands of human albumin. This study was undertaken to elucidate the structural configuration of this binding site using a photoaffinity labeling technique. Dog albumin and albumins of other animal species were photolabeled with [14C]ketoprofen. The photolabeled albumins were cleaved with cyanogen bromide (CNBr) and analyzed autoradiographically after electrophoretic separation. A 11.6-kDa CNBr fragment of the photolabeled dog albumin was found to have incorporated most of the radioactivity. Site II ligands of human albumin inhibited photoincorporation of radioactivity to this fragment. The binding constants of human and dog albumins ranged from 10 to 12 × 105 M-1, at least twice as high as those of rat, rabbit, and bovine albumins. Edman degradation was performed to elucidate the amino acid sequence of the photolabeled peptide derived from further digestion of the dog 11.6-kDa CNBr fragment with lysyl endopeptidase. The sequence was XXSESLVXRX, which corresponds to Cys476-Arg485 of dog albumin. Dog albumin contains a binding site that may have a binding microenvironment similar to that of site II on human albumin. Therefore, dog may be a better experimental animal for data extrapolation from animal to human with regard to site II drug-drug interactions.

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  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.107.016873.

  • ABBREVIATIONS: KP, ketoprofen; PAGE, polyacrylamide gel electrophoresis; CNBr, cyanogen bromide; TFA, trifluoroacetic acid; WF, warfarin; OCT, sodium octanoate; DZP, diazepam; IP, ibuprofen; HPLC, high-performance liquid chromatography; Lys-C, lysyl endopeptidase; PVDF, polyvinylidene diflouride; CD, circular dichroism; HSA, human serum albumin; UCN-01, 7-hydroxystaurosporine.

    • Received May 25, 2007.
    • Accepted October 4, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 36 (1)
Drug Metabolism and Disposition
Vol. 36, Issue 1
1 Jan 2008
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Research ArticleArticle

Subdomain IIIA of Dog Albumin Contains a Binding Site Similar to Site II of Human Albumin

Ken-ichi Kaneko, Hikaru Fukuda, Victor Tuan Giam Chuang, Keishi Yamasaki, Kohichi Kawahara, Hitoshi Nakayama, Ayaka Suenaga, Toru Maruyama and Masaki Otagiri
Drug Metabolism and Disposition January 1, 2008, 36 (1) 81-86; DOI: https://doi.org/10.1124/dmd.107.016873

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Research ArticleArticle

Subdomain IIIA of Dog Albumin Contains a Binding Site Similar to Site II of Human Albumin

Ken-ichi Kaneko, Hikaru Fukuda, Victor Tuan Giam Chuang, Keishi Yamasaki, Kohichi Kawahara, Hitoshi Nakayama, Ayaka Suenaga, Toru Maruyama and Masaki Otagiri
Drug Metabolism and Disposition January 1, 2008, 36 (1) 81-86; DOI: https://doi.org/10.1124/dmd.107.016873
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