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Biosynthesis of Novel Glucosides Geldanamycin Analogs by Enzymatic Synthesis

  • Huo, Qiang (Faculty of Pharmacy, Bengbu Medical College) ;
  • Li, Hong-Mei (Faculty of Pharmacy, Bengbu Medical College) ;
  • Lee, Jae Kyoung (Chemical Biology Research Center, KRIBB) ;
  • Li, Jing (Faculty of Pharmacy, Bengbu Medical College) ;
  • Ma, Tao (Faculty of Pharmacy, Bengbu Medical College) ;
  • Zhang, Xinyu (Faculty of Pharmacy, Bengbu Medical College) ;
  • Dai, Yiqun (Faculty of Pharmacy, Bengbu Medical College) ;
  • Hong, Young-Soo (Chemical Biology Research Center, KRIBB) ;
  • Wu, Cheng-Zhu (Faculty of Pharmacy, Bengbu Medical College)
  • Received : 2015.08.24
  • Accepted : 2015.10.09
  • Published : 2016.01.28

Abstract

Two new glucosides (1 and 2) of geldanamycin (GA) analogs were obtained from in vitro glycosylation by UDP-glycosyltransferase (YjiC). Based on spectroscopic (HR-ESI-MS, 1D, and 2D-NMR) analyses, the glucosides were elucidated as 4,5-dihydro-7-O-descarbamoyl-7-hydroxyl GA-7-O-β-D-glucoside (1) and ACDL3172-18-O-β-D-glucoside (2). Furthermore, the water solubility of compounds 1 and 2 was about 215.2 and 90.7 times higher respectively, than that of the substrates. Among compounds 1-4, only 3 showed weak antiproliferative activity against four human tumor cell lines: MDA-MB-231, SMMC7721, HepG2, and SW480 (IC50: 13.6, 15.1, 31.8, and 22.7 μM, respectively).

Keywords

References

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