Dynamic Covalent Identification of an Efficient Heparin Ligand

Miriam Corredor, Daniel Carbajo, Cecilia Domingo, Yolanda Pérez, Jordi Bujons, Angel Messeguer, Ignacio Alfonso
2018 Angewandte Chemie  
Despite heparin being the most widely used macromolecular drug, the design of small-molecule ligands to modulate its effects has been hampered by the structural properties of this polyanionic polysaccharide. In this work we used a dynamic covalent selection approach to identify a new ligand for heparin, assembled from extremely simple building blocks. The amplified molecule strongly binds to heparin (KD in the low M range, ITC) by a combination of electrostatic, hydrogen bonding and CH-π
more » ... ctions as shown by NMR and molecular modeling. Moreover, this ligand reverts the inhibitory effect of heparin within an enzymatic cascade reaction related to blood coagulation. Our study demonstrates the power of dynamic covalent chemistry for the discovery of new modulators of biologically relevant glycosaminoglycans. [a]
doi:10.1002/ange.201806770 fatcat:e3biy76airewnk45cfm5dfknfy