Abstract
Summary: Heparin, the well‐known anticoagulant polysaccharide, is also active in many other biological systems owing to its structural similarity to HS, but usually lacks selectivity because it is more highly sulfated. A series of straightforward chemical reactions (de‐O‐sulfation, de‐N‐sulfation and re‐N‐acetylation), carried out to partial or complete extent, were combined, resulting in a number of modified heparin polysaccharide derivatives with altered properties. These exhibited a range of abilities to promote cell signalling through the FGF/FGFR tyrosine kinase signalling system, in an in vitro cell assay with combinations of FGF‐1, ‐2, ‐3 and FGFR 1 and 3. One polysaccharide (N‐acetylated, 6‐O‐ and 2‐O‐sulfated heparin), with only a fraction (<10^−3^) of the anticoagulant activity of heparin (200 U · mg^−1^), promoted FGF‐2‐mediated angiogenesis (10‐fold) and therefore had an improved ratio of pro‐angiogenic activity to anticoagulant activity in excess of 10^4^ compared to heparin. These results demonstrate that heparin‐derived polysaccharides can be engineered for selected activities and have potential in a wide range of medical, biotechnological and tissue‐engineering applications.
Effect of selected engineered heparin polysaccharides on angiogenesis.
magnified imageEffect of selected engineered heparin polysaccharides on angiogenesis.