摘要
肺结核依然是一个致命的感染性疾病,主要是由于长效的细菌群的存在,能够在药物治疗中存活和阻碍完整的感染根除。GlgB和GlgE酶包含在葡聚糖通路,最近被确定为有前景的药物靶点用于抗击持久的芽泡杆菌。在葡聚糖通路中,酶GlgB,GlgE 和Tre-xyz产生线性的α-葡聚糖,能够通过GlgB转化为必要的支链α-葡聚糖。这个α-葡聚糖是个重要的细胞壁和保存多聚糖,在Mtb的毒性和持久性有着重要作用。我们重点介绍当前GlgB和GlgE在葡聚糖信号通路中的重要性视角,并讨论了结核病的药物治疗策略,如针对GlgB和GlgE的复合药理学。本文也讨论了以小分子为基础的能调节GlgB和GlgE的观点使得新的、改进药物设计和开发得到发展,以达到更好的选择性和针对肺结核的有效性。
关键词: α-葡聚糖,荚膜葡聚糖,GlgB,GlgE,糖原枝化酶,高通量的筛选测试,辣根过氧化酶测试,碘酒测试,Mtb,复合药理学,小分子
Current Medicinal Chemistry
Title:α-Glucan Pathway as a Novel Mtb Drug Target: Structural Insights and Cues for Polypharmcological Targeting of GlgB and GlgE
Volume: 21 Issue: 35
Author(s): Pushpa Agrawal, Pawan Gupta, Kunchithapadam Swaminathan and Raman Parkesh
Affiliation:
关键词: α-葡聚糖,荚膜葡聚糖,GlgB,GlgE,糖原枝化酶,高通量的筛选测试,辣根过氧化酶测试,碘酒测试,Mtb,复合药理学,小分子
摘要: Tuberculosis continues to be a deadly infectious disease, mainly due to the existence of persistent bacterial populations that survive drug treatment and obstruct complete eradication of infection. The enzymes GlgE and GlgB, which are involved in the glycan pathway, have recently been identified as promising drug targets for combating persistent bacillus strains. In the glycan pathway, enzymes GlgE, GlgA, and Tre-xyz produce linear α-glucans, which are then converted to essential branched α-glucan by GlgB. This α-glucan is a vital cell-wall and storage polysaccharide, critical for Mtb virulence and persistence. We highlight recent insights into the significance of both GlgE and GlgB in the glycan pathway and also discuss drug strategies for tuberculosis such as polypharmcological targeting of GlgB and GlgE. Small molecule-based modulation of GlgB and GlgE to boost the design and development of novel and improved drugs for more selective and efficient targeting of tuberculosis are also discussed.
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Cite this article as:
Agrawal Pushpa, Gupta Pawan, Swaminathan Kunchithapadam and Parkesh Raman, α-Glucan Pathway as a Novel Mtb Drug Target: Structural Insights and Cues for Polypharmcological Targeting of GlgB and GlgE, Current Medicinal Chemistry 2014; 21 (35) . https://dx.doi.org/10.2174/0929867321666140826120449
DOI https://dx.doi.org/10.2174/0929867321666140826120449 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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