Analysis of the neutral polysaccharide fraction of MCP and its inhibitory activity on galectin-3
Analysis of the neutral polysaccharide fraction of MCP and its inhibitory activity on galectin-3
复制标题
MCP中性多糖组分分析及其对galectin-3的抑制活性
DOI：
10.1007/s10719-012-9382-5
复制
发表时间：
2012-05-01
影响因子：
3
通讯作者：
Zhou, Yifa
中科院分区：
文献类型：
--
作者：
Gao, Xiaoge;Zhi, Yuan;Zhou, Yifa
已经证明pH改性的柑橘果胶（MCP）在癌症进展中抑制半乳糖凝集素-3。与这种抑制作用有关的MCP的组分和结构尚不清楚。在本文中，我们在DEAE-纤维素柱上分离MCP为均匀的中性级分MCP-N（约20 kDa）和果胶混合级分MCP-A（SepharoseCL-6 B色谱上的宽分子分布）。MCP-N和MCP-A均能抑制galectin-3介导的血凝反应，最低抑制浓度（MIC）分别为625和0.5 μg/ml。MCP-N经鉴定为Ⅰ型阿拉伯半乳聚糖（AG-I），主链为β-1 β 4-半乳聚糖。MCP-N经α-L-阿拉伯呋喃糖苷酶酶解后，其主链结构部分（M-galactan，约18 kDa）比原分子活性更高，MIC为50 μg/ml。半乳聚糖的酸性降解使其抑菌活性增强，MIC比半乳聚糖低5倍左右。上述结果表明，β-1 β 4-半乳聚糖片段的功能基序可能位于链的末端残基，而不是链的内部区域。因此，MCP-N及其降解产物有可能被开发为新的潜在的半乳糖凝集素-3抑制剂。这是首次报道MCP及其组分对半乳糖凝集素-3的抑制作用。本研究为从天然多糖中筛选活性更高的galectin-3抑制剂提供了参考。
The pH-modified citrus pectin (MCP) has been demonstrated to inhibit galectin-3 in cancer progression. The components and structures of MCP related to this inhibition remained unknown. In this paper, we fractionated MCP on DEAE-cellulose column into a homogenous neutral fraction MCP-N (about 20 kDa) and a pectin mixture fraction MCP-A (wide molecular distribution on Sepharose CL-6B chromatography). Both MCP-N and MCP-A inhibited hemagglutination mediated by galectin-3 with minimum inhibition concentration (MIC) 625 and 0.5 μg/ml, respectively. MCP-N was identified to be a type I arabinogalactan (AG-I) with a main chain of β-1→4-galactan. MCP-N was digested by α-L-arabinofuranosidase to give its main chain structure fraction (M-galactan, around 18 kDa), which was more active than the original molecule, MIC 50 μg/ml. The acidic degradation of M-galactan increased the inhibitory activity, MIC about 5 times lower than M-galactan. These results above showed that the functional motif of the β-1→4-galactan fragment might lie in the terminal residues rather than in the internal region of the chain. Therefore, MCP-N and its degraded products might be developed to new potential galectin-3 inhibitors. This is the first report concerning the fractionation of MCP and its components on galectin-3 inhibition. The information provided in this paper is valuable for screening more active galectin-3 inhibitors from natural polysaccharides.