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Enzymatic synthesis of lactosylated and sialylated derivatives of epothilone A

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Abstract

Epothilone A is a derivative of 16-membered polyketide natural product, which has comparable chemotherapeutic effect like taxol. Introduction of sialic acids to these chemotherapeutic agents could generate interesting therapeutic glycoconjugates with significant effects in clinical studies. Since, most of the organisms biosynthesize sialic acids in their cell surface, they are key mediators in cellular events (cell-cell recognition, cell-matrix interactions). Interaction between such therapeutic sugar parts and cellular polysaccharides could generate interesting result in drugs like epothilone A. Based on this hypothesis, epothilone A glucoside (epothilone A 6-O-β-D-glucoside) was further decorated by conjugating enzymatically galactose followed by sialic acids to generate epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactoside i.e., lactosyl epothilone A (lac epoA) and two sialosides of epothilone A namely epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactopyranosyl 3″-O-α-N-acetyl neuraminic acid and epothilone A 7-O-β-D-glucopyranosyl, 4′-O-α-D-galactopyranosyl 6″-O-α-N-acetylneuraminic acid i.e., 3′sialyllactosyl epothilone A: 3′SL-epoA, and 6′sialyllactosyl epothilone A: 6′SL-epoA, respectively. These synthesized analogs were spectroscopically analyzed and elucidated, and biologically validated using HUVEC and HCT116 cancer cell lines.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF-2014R1A2A2A01002875).

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Authors and Affiliations

  1. Institute of Biomolecule Reconstruction, Department of BT-convergent Pharmaceutical Engineering, SunMoon University, 70, Sun Moon-Ro 221, Tangjeonmyun, Asan-Si, Chungnam, 336-708, South Korea

    Prakash Parajuli, Ramesh Prasad Pandey, Rit Bahadur Gurung, Ju Yong Shin, Hye Jin Jung & Jae Kyung Sohng

  2. GeneChem, 59-5, Jang-dong, Yuseong-gu, Daejeon, 305-343, South Korea

    Dae Hee Kim

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  1. Prakash Parajuli
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Correspondence to Jae Kyung Sohng.

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Parajuli, P., Pandey, R.P., Gurung, R.B. et al. Enzymatic synthesis of lactosylated and sialylated derivatives of epothilone A. Glycoconj J 33, 137–146 (2016). https://doi.org/10.1007/s10719-015-9646-y

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  • DOI: https://doi.org/10.1007/s10719-015-9646-y

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