title: Enzymatic synthesis of lactosylated and sialylated derivatives of epothilone A.
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.
authors: 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.
authors: Prakash
authors: P
authors: Parajuli
authors: 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.
authors: Ramesh Prasad
authors: RP
authors: Pandey
authors: 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.
authors: Rit Bahadur
authors: RB
authors: Gurung
authors: 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.
authors: Ju Yong
authors: JY
authors: Shin
authors: 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.
authors: Hye Jin
authors: HJ
authors: Jung
authors: GeneChem, 59-5, Jang-dong, Yuseong-gu, Daejeon, 305-343, South Korea.
authors: Dae Hee
authors: DH
authors: Kim
authors: 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. sohng@sunmoon.ac.kr.
authors: Jae Kyung
authors: JK
authors: Sohng
mesh_terms: D045744:Cell Line, Tumor; D034261:Epothilones / Q000493:pharmacokinetics / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*
chemical_list: D034261:Epothilones; D019344:Lactic Acid; C093787:epothilone A; D019158:N-Acetylneuraminic Acid
keywords: 3′Sialyllactosyl epothilone A; 6′sialyllactosyl epothilone A; Chemotherapeutic agent; Epothilone A 6-O-β-D-glucoside; Epothilones