α-葡聚糖通路作为一个新颖的Mtb药物靶标：针对GlgB和GlgE的复合药理学的结构视角和依据

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.

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