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Title: | EXAMINATION OF THE STRUCTURAL DETERMINANTS OF HEPARIN/HEPARAN SULPHATE-TGF-B1 INTERACTIONS AND THEIR THERAPEUTIC APPLICATIONS | Authors: | JONATHAN LEE HOUJIN | Keywords: | Transforming Growth Factor-beta 1, Heparan Sulphate, Heparin, Cartilage, Glycobiology, Mesenchymal stem cell | Issue Date: | 10-Nov-2014 | Citation: | JONATHAN LEE HOUJIN (2014-11-10). EXAMINATION OF THE STRUCTURAL DETERMINANTS OF HEPARIN/HEPARAN SULPHATE-TGF-B1 INTERACTIONS AND THEIR THERAPEUTIC APPLICATIONS. ScholarBank@NUS Repository. | Abstract: | HEPARAN SULPHATES (HS) ARE HIGHLY SULPHATED, LINEAR POLYSACCHARIDES THAT ARE A MAJOR COMPONENT OF THE EXTRACELLULAR MATRIX. THEIR INNATE ABILITY TO BIND, STABILISE AND POTENTIATE A RANGE OF BIOLOGICALLY RELEVANT PROTEINS, WHILE REMAINING STABLE THEMSELVES OVER PROLONGED PERIODS, MAKES THEM IDEALLY SUITED FOR THE DEVELOPMENT OF OFF-THE-SHELF THERAPIES. HERE WE REPORT THE IDENTIFICATION OF THE STRUCTURAL DETERMINANTS OF THE HEPARIN-TGF-?1 INTERACTION, AND THE SUBSEQUENT DEVELOPMENT OF AN HS VARIANT WITH TARGETED AFFINITY FOR TGF-?1, SUBSEQUENTLY TERMED HS16+VE. APPLICATION OF THIS HS WAS POSITED TO BIND AND POTENTIATE THE ACTIVITY OF ENDOGENOUS TGF-?1 PRESENT AT THE SITE OF CARTILAGE INJURY, SO REMOVING THE NEED FOR ITS EXOGENOUS APPLICATION. THE WORK PRESENTED HERE ALLOWS ONE TO ASSERT THAT SUCH HEPARIN:HS COMPARISONS CAN SERVE AS EFFICIENT TEMPLATES FOR THE DEVELOPMENT OF HS VARIANTS FOR OTHER CLINICALLY RELEVANT GROWTH FACTORS. IT ALSO PAVES THE WAY FOR FURTHER STUDIES OF TGF-?1-HS | URI: | http://scholarbank.nus.edu.sg/handle/10635/119033 |
Appears in Collections: | Ph.D Theses (Open) |
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