Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Structural Analysis of 5-aminosalicyl-L-glutamic Acid, a Colon-specific Prodrug of 5-aminosalicylic Acid, for Colon-specific Deconjugation

  • Received : 2010.06.09
  • Accepted : 2010.07.27
  • Published : 2010.08.20
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Abstract

In a previous paper, we showed that 5-aminosalicyl-L-aspartic acid (5-ASA-Asp) has much greater deconjugation efficiency in the cecal contents than does 5-aminosalicyl-L-glutamic acid (5-ASA-Glu). To explore a reason for ineffective deconjugation of 5-ASA-Glu, structural analysis of the conjugate was performed. Aromatic acyl-L-glutamic acid derivatives, N-benzoyl-glumatic acid (BA-Glu), N-(2-hydroxybenzoyl)-glutamic acid (SA-Glu), N-(3-aminobenzoyl)-glutamic acid (3-ABA-Glu) and N-(4-aminobenzoyl)-glutamic acid (4-ABA-Glu), were prepared and incubated in the cecal contents. The deconjugation rates were compared with that of 5-ASA-Glu. The order of the rates was BA-Glu $\approx$ 4-ABA-Glu $\approx$ 3-ABA-Glu $\gg$ SA-Glu $\approx$ 5-ASA-Glu. The deconjugation of the aromatic acyl-L-glutamic acid derivatives was carried out by enzyme(s) in the cecal contents since the deconjugation did not occur in the autoclaved cecal contents and on incubation with N-benzoyl-D-glutamic acid. Our data suggest that the 2-hydroxyl group in 5-ASA is ascribed to the poor deconjugation of 5-ASA-Glu in the cecal contents.

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