Differences in the mannose oligomer specificities of the closely related lectins from Galanthus nivalis and Zea mays strongly determine their eventual anti-HIV activity.
Differences in the mannose oligomer specificities of the closely related lectins from Galanthus nivalis and Zea mays strongly determine their eventual anti-HIV activity.
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DOI：
10.1186/1742-4690-8-10
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发表时间：
2011-02-11
期刊：
影响因子：
3.3
通讯作者：
Balzarini J
中科院分区：
文献类型：
--
作者：
Hoorelbeke B;Van Damme EJ;Rougé P;Schols D;Van Laethem K;Fouquaert E;Balzarini J
在最近的一份报告中，通过Glycan阵列分析确定了植物讲座的植物讲座（GNA）（GNA）的碳水化结合规格和Zea Mays（Gnamaize）的密切相关的讲座对高曼诺斯型糖的特异性。
GNAMAIZE似乎比GNA对HIV感染，持续的HIV-1感染的HUT-78细胞与未感染的CD4+ T-淋巴细胞SUPT1细胞，HIV-1在DC-SIGN和DC-SIGN和未感染的CD4+ T-SUPT1细胞之间形成抑制性〜20至100倍。随后向未感染的CD4+ T淋巴细胞传播DC签名的病毒与GNA相反，该病毒优先选择具有已删除的病毒在GP120上，高频型聚糖，将HIV-1长时间暴露于剂量降低的GNAMAIZE浓度，以用于突变病毒菌株，其中一种复合物型GP120均删除了GP120。 GNAMAIZE与HIV IIIB GP120相互作用，分别为0.33 nm和34 nm的亲和力常数（KD）。选择性结合复合型GlcNACβ1,2MAN低聚物。特异性）或sna（neuacα2,6x比）。
与GNA相比，GNAMAIZE的抗HIV活性显着降低，可以通过聚糖识别的深刻变化以及Gnamaize中碳水化合物结合位点的消失，而Gnamaize的碳水化合物结合位点对甘露糖的低聚物具有很高的亲和力。赋予抗HIV活性的疗法，而化学治疗剂与GP120的甘露糖的甘露糖结合可能会导致明显对病毒的活性中和。
In a recent report, the carbohydrate-binding specificities of the plant lectins Galanthus nivalis (GNA) and the closely related lectin from Zea mays (GNAmaize) were determined by glycan array analysis and indicated that GNAmaize recognizes complex-type N-glycans whereas GNA has specificity towards high-mannose-type glycans. Both lectins are tetrameric proteins sharing 64% sequence similarity. GNAmaize appeared to be ~20- to 100-fold less inhibitory than GNA against HIV infection, syncytia formation between persistently HIV-1-infected HuT-78 cells and uninfected CD4+ T-lymphocyte SupT1 cells, HIV-1 capture by DC-SIGN and subsequent transmission of DC-SIGN-captured virions to uninfected CD4+ T-lymphocyte cells. In contrast to GNA, which preferentially selects for virus strains with deleted high-mannose-type glycans on gp120, prolonged exposure of HIV-1 to dose-escalating concentrations of GNAmaize selected for mutant virus strains in which one complex-type glycan of gp120 was deleted. Surface Plasmon Resonance (SPR) analysis revealed that GNA and GNAmaize interact with HIV IIIB gp120 with affinity constants (KD) of 0.33 nM and 34 nM, respectively. Whereas immobilized GNA specifically binds mannose oligomers, GNAmaize selectively binds complex-type GlcNAcβ1,2Man oligomers. Also, epitope mapping experiments revealed that GNA and the mannose-specific mAb 2G12 can independently bind from GNAmaize to gp120, whereas GNAmaize cannot efficiently bind to gp120 that contained prebound PHA-E (GlcNAcβ1,2man specific) or SNA (NeuAcα2,6X specific). The markedly reduced anti-HIV activity of GNAmaize compared to GNA can be explained by the profound shift in glycan recognition and the disappearance of carbohydrate-binding sites in GNAmaize that have high affinity for mannose oligomers. These findings underscore the need for mannose oligomer recognition of therapeutics to be endowed with anti-HIV activity and that mannose, but not complex-type glycan binding of chemotherapeutics to gp120, may result in a pronounced neutralizing activity against the virus.
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影响因子：
5.4
作者：
Balzarini, J;Van Laethem, K;Schols, D
通讯作者：
Schols, D
影响因子：
3.6
作者：
Balzarini, J;Van Laethem, K;Schols, D
通讯作者：
Schols, D
影响因子：
4.9
作者：
Balzarini, Jan;Francois, Katrien O.;Schols, Dominique
通讯作者：
Schols, Dominique
影响因子：
56.9
作者：
GHIARA, JB;STURA, EA;WILSON, IA
通讯作者：
WILSON, IA
来自雪花莲和玉米的相关凝集素在碳水化合物结合特异性上有所不同。
DOI：
10.1016/j.bbrc.2009.01.048
发表时间：
2009-03-06
影响因子：
3.1
作者：
Fouquaert, Elke;Smith, David F.;Peumans, Willy J.;Proost, Paul;Balzarini, Jan;Savvides, Savvas N.;Van Damme, Els J. M.
通讯作者：
Van Damme, Els J. M.