Synthesis of deoxygenated alpha(1 -> 5)-linked arabinofuranose disaccharides as substrates and inhibitors of arabinosyltransferases of Mycobacterium tuberculosis

AK Pathak; V Pathak; WJ Suling; JR Riordan; Sudagar Gurcha; Gurdyal Besra; RC Reynolds

doi:10.1016/j.bmc.2008.11.027

Synthesis of deoxygenated alpha(1 -> 5)-linked arabinofuranose disaccharides as substrates and inhibitors of arabinosyltransferases of Mycobacterium tuberculosis

AK Pathak, V Pathak, WJ Suling, JR Riordan, Sudagar Gurcha, Gurdyal Besra, RC Reynolds

Biosciences

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19 Citations (Scopus)

Abstract

Arabinosyltransferases (AraTs) play a critical role in mycobacterial cell wall biosynthesis and are potential drug targets for the treatment of tuberculosis, especially multi-drug resistant forms of M. tuberculosis (MTB). Herein, we report the synthesis and acceptor/inhibitory activity of Araf alpha(1 -> 5) Araf disaccharides possessing deoxygenation at the reducing sugar of the disaccharide. Deoxygenation at either the C-2 or C-3 position of Araf was achieved via a free radical procedure using xanthate derivatives of the hydroxyl group. The alpha(1 -> 5)-linked disaccharides were produced by coupling n-octyl alpha-Araf 2-/3-deoxy, 2-fluoro glycosyl acceptors with an Araf thioglycosyl donor. The target disaccharides were tested in a cell free mycobacterial AraTs assay as well as an in vitro assay against MTB H37Ra and M. avium complex strains. (C) 2008 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	872-881
Number of pages	10
Journal	Bioorganic & Medicinal Chemistry
Volume	17
Issue number	2
DOIs	https://doi.org/10.1016/j.bmc.2008.11.027
Publication status	Published - 1 Jan 2009

Keywords

Deoxyarabinofuranose
2-Fluoroarabinofuranose
Inhibitors
Arabinosyltransferases
Mycobacterium tuberculosis
Disaccharides

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2008.11.027

MAGPIE Project: The Structure and Assembly of the Mycobacterial Cell Envelope
Besra, D., Lammas, T. & Minnikin, D.
Medical Research Council
1/02/06 → 31/01/11
Project: Research Councils

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title = "Synthesis of deoxygenated alpha(1 -> 5)-linked arabinofuranose disaccharides as substrates and inhibitors of arabinosyltransferases of Mycobacterium tuberculosis",

abstract = "Arabinosyltransferases (AraTs) play a critical role in mycobacterial cell wall biosynthesis and are potential drug targets for the treatment of tuberculosis, especially multi-drug resistant forms of M. tuberculosis (MTB). Herein, we report the synthesis and acceptor/inhibitory activity of Araf alpha(1 -> 5) Araf disaccharides possessing deoxygenation at the reducing sugar of the disaccharide. Deoxygenation at either the C-2 or C-3 position of Araf was achieved via a free radical procedure using xanthate derivatives of the hydroxyl group. The alpha(1 -> 5)-linked disaccharides were produced by coupling n-octyl alpha-Araf 2-/3-deoxy, 2-fluoro glycosyl acceptors with an Araf thioglycosyl donor. The target disaccharides were tested in a cell free mycobacterial AraTs assay as well as an in vitro assay against MTB H37Ra and M. avium complex strains. (C) 2008 Elsevier Ltd. All rights reserved.",

keywords = "Deoxyarabinofuranose, 2-Fluoroarabinofuranose, Inhibitors, Arabinosyltransferases, Mycobacterium tuberculosis, Disaccharides",

author = "AK Pathak and V Pathak and WJ Suling and JR Riordan and Sudagar Gurcha and Gurdyal Besra and RC Reynolds",

year = "2009",

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doi = "10.1016/j.bmc.2008.11.027",

language = "English",

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journal = "Bioorganic & Medicinal Chemistry",

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T1 - Synthesis of deoxygenated alpha(1 -> 5)-linked arabinofuranose disaccharides as substrates and inhibitors of arabinosyltransferases of Mycobacterium tuberculosis

AU - Pathak, AK

AU - Pathak, V

AU - Suling, WJ

AU - Riordan, JR

AU - Gurcha, Sudagar

AU - Besra, Gurdyal

AU - Reynolds, RC

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Arabinosyltransferases (AraTs) play a critical role in mycobacterial cell wall biosynthesis and are potential drug targets for the treatment of tuberculosis, especially multi-drug resistant forms of M. tuberculosis (MTB). Herein, we report the synthesis and acceptor/inhibitory activity of Araf alpha(1 -> 5) Araf disaccharides possessing deoxygenation at the reducing sugar of the disaccharide. Deoxygenation at either the C-2 or C-3 position of Araf was achieved via a free radical procedure using xanthate derivatives of the hydroxyl group. The alpha(1 -> 5)-linked disaccharides were produced by coupling n-octyl alpha-Araf 2-/3-deoxy, 2-fluoro glycosyl acceptors with an Araf thioglycosyl donor. The target disaccharides were tested in a cell free mycobacterial AraTs assay as well as an in vitro assay against MTB H37Ra and M. avium complex strains. (C) 2008 Elsevier Ltd. All rights reserved.

AB - Arabinosyltransferases (AraTs) play a critical role in mycobacterial cell wall biosynthesis and are potential drug targets for the treatment of tuberculosis, especially multi-drug resistant forms of M. tuberculosis (MTB). Herein, we report the synthesis and acceptor/inhibitory activity of Araf alpha(1 -> 5) Araf disaccharides possessing deoxygenation at the reducing sugar of the disaccharide. Deoxygenation at either the C-2 or C-3 position of Araf was achieved via a free radical procedure using xanthate derivatives of the hydroxyl group. The alpha(1 -> 5)-linked disaccharides were produced by coupling n-octyl alpha-Araf 2-/3-deoxy, 2-fluoro glycosyl acceptors with an Araf thioglycosyl donor. The target disaccharides were tested in a cell free mycobacterial AraTs assay as well as an in vitro assay against MTB H37Ra and M. avium complex strains. (C) 2008 Elsevier Ltd. All rights reserved.

KW - Deoxyarabinofuranose

KW - 2-Fluoroarabinofuranose

KW - Inhibitors

KW - Arabinosyltransferases

KW - Mycobacterium tuberculosis

KW - Disaccharides

U2 - 10.1016/j.bmc.2008.11.027

DO - 10.1016/j.bmc.2008.11.027

M3 - Article

C2 - 19056279

VL - 17

SP - 872

EP - 881

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 2

ER -

Synthesis of deoxygenated alpha(1 -> 5)-linked arabinofuranose disaccharides as substrates and inhibitors of arabinosyltransferases of Mycobacterium tuberculosis

Abstract

Keywords

UN SDGs

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Projects

MAGPIE Project: The Structure and Assembly of the Mycobacterial Cell Envelope

Cite this