设计、合成及评价硫酸乙酰肝素模拟糖聚合物抑制乙酰肝素酶活性。
Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity.
机构信息
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA.
出版信息
Chem Commun (Camb). 2017 Aug 10;53(65):9163-9166. doi: 10.1039/c7cc04156j.
Abstract
Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, a glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics. This glycopolymer also lacks anticoagulant activity.
摘要
肝素酶是一种能够切割细胞外基质中硫酸乙酰肝素（HS）多糖的酶。它是肿瘤行为的调节剂，在肾脏相关疾病和自身免疫性糖尿病中发挥着关键作用。我们在此报告了使用计算研究来提取天然 HS-肝素酶相互作用作为设计 HS 模拟糖聚物的模板。经评估，具有 12 个重复单元的糖聚物被确定为最有效的抑制剂，并具有紧密结合的特性。这种糖聚物也缺乏抗凝血活性。
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