Synthesis and antiherpetic activity of carboxymethylated and sulfated hyaluronan derivatives
Synthesis and antiherpetic activity of carboxymethylated and sulfated hyaluronan derivatives
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DOI：
10.1016/j.carbpol.2012.05.085
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发表时间：
2012-09-01
影响因子：
11.2
通讯作者：
Schnabelrauch, Matthias
中科院分区：
文献类型：
--
作者：
Moeller, Stephanie;Schmidtke, Michaela;Schnabelrauch, Matthias
天然高分子量透明质酸（HMW-HA, M-W = 1 × 10(6) g/mol）和热降解低分子量透明质酸（LMW-HA, M-W = 1.3-1.4 × 10(5) g/mol）被羧甲基化，产品的羧甲基化度（DSCM）高达0.8。通过不同的磺化程序对得到的羧甲基透明质酸（CM-HA）和透明质酸（HA）进行磺化，使得到的新的羧甲基透明质酸硫酸盐（CM-HA- s）和透明质酸硫酸盐（HA- s）的磺化度（DSS）分别控制在0.9和3.3之间。羧甲基化和硫酸化都优先发生在HA的一级羟基上。这些合成的透明质酸衍生物对1型单纯疱疹病毒的抗病毒活性进行了测试。HA-S和CM-HA-S衍生物均表现出较强的抗疱疹活性，其DSS值约为3.0。CM-HA- s衍生物没有活性，引入羧甲基对CM-HA- s衍生物的抗疱疹活性没有额外的影响。HA-S的抗病毒效果与DSs相关，且随着DSs值的增大而增强。(C) 2012 Elsevier Ltd.版权所有。
Native high molecular weight hyaluronan (HMW-HA, M-W = 1 x 10(6) g/mol) and a thermally degraded low molecular weight hyaluronan (LMW-HA, M-W = 1.3-1.4 x 10(5) g/mol) were carboxymethylated providing products with degrees of carboxymethylation (DSCM) of up to 0.8. Sulfation of resulting carboxymethyl hyaluronan (CM-HA) and hyaluronan (HA) was performed by different sulfation procedures enabling the control of the degree of sulfation (DSS) in the obtained new carboxymethyl hyaluronan sulfates (CM-HA-S) and hyaluronan sulfates (HA-S), respectively, in a range between 0.9 and 3.3. Both carboxymethylation and sulfation were found to take place preferentially at the primary hydroxyl groups of HA. The antiviral activity of these synthesized HA derivatives was tested against Herpes simplex virus type 1. Both HA-S and CM-HA-S derivatives with high DSS values of about 3.0 exhibit a strong antiherpetic activity. The CM-HA derivatives were found to be not active and an additional effect of introduced carboxymethyl groups on the antiherpetic activity of CM-HA-S derivatives was not observed. In the case of HA-S, the antiviral efficacy can be correlated with the DSs and becomes stronger with increasing DSs values. (C) 2012 Elsevier Ltd. All rights reserved.