Dr John Gardiner: paper publised in Nature Communications

A faster new ‘4x4' route to long synthetic heparins provides first in vivo PK studies.

A faster new ‘4x4' route to long synthetic heparins provides first in vivo PK studies. (DOI:10.1038/ncomms3016) reports a new strategy to accelerate access to long synthetic heparin-like oligosaccharides and use for preclinical PK. Investigating the potential for new heparin-like glycosaminoglycan (GAGs) therapeutics has been limited by the challenges facing synthesis of such oligosaccharides, with few reports to milligram-scale synthesis of bioactive 10 or 12-mer sequences. The Gardiner group recently reported a jump to gram scale access to H/HS-like dodecasacccharides. This new paper, the work of postdocs Gavin Miller and Steen Hansen, funded by MRC DFPS and CRUK DC grants, reports a new tetrasaccharide block approach to dodecasaccharide in just two homologation cycles (4x4x4), significantly accelerating accessibility. Inclusion of a releasable end-group for late-stage labeling, provides the first example of distribution and PK studies using any homogenous, bioactive heparin-related oligosaccharide, underpinning the translational potential of pure synthetic heparanoid drugs.                                     

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