Unknown

Dataset Information

0

Chemoenzymatic synthesis of homogeneous ultralow molecular weight heparins.


ABSTRACT: Ultralow molecular weight (ULMW) heparins are sulfated glycans that are clinically used to treat thrombotic disorders. ULMW heparins range from 1500 to 3000 daltons, corresponding from 5 to 10 saccharide units. The commercial drug Arixtra (fondaparinux sodium) is a structurally homogeneous ULMW heparin pentasaccharide that is synthesized through a lengthy chemical process. Here, we report 10- and 12-step chemoenzymatic syntheses of two structurally homogeneous ULMW heparins (MW = 1778.5 and 1816.5) in 45 and 37% overall yield, respectively, starting from a simple disaccharide. These ULMW heparins display excellent in vitro anticoagulant activity and comparable pharmacokinetic properties to Arixtra, as demonstrated in a rabbit model. The chemoenzymatic approach is scalable and shows promise for a more efficient route to synthesize this important class of medicinal agent.

SUBMITTER: Xu Y 

PROVIDER: S-EPMC3425363 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5412866 | BioStudies
| S-EPMC4477280 | BioStudies
2014-01-01 | S-EPMC4393012 | BioStudies
2019-01-01 | S-EPMC6585337 | BioStudies
1000-01-01 | S-EPMC3976284 | BioStudies
| S-EPMC5953189 | BioStudies
| S-EPMC5067489 | BioStudies
2017-01-01 | S-EPMC6152090 | BioStudies
2010-01-01 | S-EPMC3717399 | BioStudies
| S-EPMC7486512 | BioStudies