Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Solubilization of Pyrimethamine, Antibacterial Drug, by Low-Molecular-Weight Succinoglycan Dimers Isolated from Shinorhizobium meliloti

  • Kim, Hwan-Hee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University) ;
  • Kim, Kyoung-Tea (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University) ;
  • Choi, Jae-Min (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University) ;
  • Tahir, Muhammad Nazir (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University) ;
  • Cho, Eun-Ae (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University) ;
  • Choi, Young-Jin (BioChip Research Center, Hoseo University) ;
  • Lee, Im-Soon (Department of Biological Sciences & Center for Biotechnology Research in UBITA, Konkuk University) ;
  • Jung, Seun-Ho (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Center for Biotechnology Research in UBITA, Konkuk University)
  • Received : 2012.05.17
  • Accepted : 2012.05.23
  • Published : 2012.08.20
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Abstract

The use of pyrimethamine as antibacterial drug is limited by the poor solubility. To enhance its solubility, we prepared complexes of pyrimethamine with low-molecular-weight succinoglycan isolated from Sinorhizobium meliloti. Low-molecular-weight succinoglycans are monomers, dimers, and trimers of the succinoglycan repeating unit. The monomers and dimers were separated into their three species (M1, M2, and M3) and four fractions (D1 to D4) using chromatographic techniques, which were shown to be nontoxic. The solubility of pyrimethamine was markedly increased up to 42 fold by succinoglycan D3, where the level of its solubility enhancement was even 8-20 fold higher comparing with cyclodextrin or its derivatives. The complex formation of succinoglycan D3 with pyrimethamine was confirmed by $^1H$ nuclear magnetic resonance spectroscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and molecular modeling studies. Herein, we suggest that the low-molecular-weight succinoglycans may be utilized as highly effective solubilizers of pyrimethamine for pharmaceutical purposes.

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