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Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity.

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.

SUBMITTER: Loka RS

PROVIDER: S-EPMC5590105 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity.

Loka Ravi S RS Yu Fei F Sletten Eric T ET Nguyen Hien M HM

Chemical communications (Cambridge, England) 20170801 65

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 c ...[more]

PMID: 28766595

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