Rational design of low-molecular weight heparins with improved in vivo activity
Massachusetts Institute of Technology
Robert Langer's group at MIT demonstrates a practical analytical method enabling measurement of a structural correlate to in vivo anticoagulant function.They have used this information to to develop low-molecular weight heparins (LMWHs) with increased anticoagulant activity and decreased polydispersity. Desirable in vivo pharmacokinetic properties and the ability to cause release of tissue factor pathway inhibitor from the endothelium are among several beneficial aspects of these LMWHs. The findings demonstrate a simple approach for the creation of designer LMWHs. The group used their miniDAWN in conjunction with a Shodex HPLC system to determine the molar mass and polydispersity of their heparins.
Sundaram, M.; Qi, Y.; Shriver, Z.; Liu, D.; Zhao, G.; Venkataraman, G.; Langer, R.; Sasisekharan, R. PNAS 2003, 100, 651-656. DOI: 10.1073/pnas.252643299