Molecularly imprinted microgels as enzyme inhibitors.
We demonstrate, on the example of trypsin, the use of water-soluble molecularly imprinted polymer microgels as specific enzyme inhibitors. Using a strong anchoring monomer, methacryloylaminobenzamidine, the growing polymer chains are confined to close proximity of the substrate recognition site of our model enzyme. The microgels bind selectively trypsin over other proteins of similar size and molecular weight, and show competitive inhibition of trypsin with an inhibition constant K(i) of 79 nM, making them more potent inhibitors than the low molecular-weight competitive inhibitor benzamidine by almost 3 orders of magnitude. We believe that these tailor-made materials with biological activity have potential for future drug development that extends beyond enzyme inhibition.
Department of Bioengineering, Compiègne University of Technology, UMR CNRS 6022, France.
Arnaud
A
Cutivet
Carol
C
Schembri
Jose
J
Kovensky
Karsten
K
Haupt
D001550:Benzamidines / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005782:Gels; D054802:Molecular Imprinting; D008970:Molecular Weight; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D001550:Benzamidines; D004791:Enzyme Inhibitors; D005782:Gels; D011108:Polymers; D014361:Trypsin Inhibitors; C032157:benzamidine