RESUMO
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.
Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Polímeros/síntese química , Polímeros/farmacologia , Benzamidinas/química , Inibidores Enzimáticos/química , Géis , Impressão Molecular , Peso Molecular , Polímeros/química , Inibidores da Tripsina/síntese química , Inibidores da Tripsina/química , Inibidores da Tripsina/farmacologiaRESUMO
A new approach is proposed for the synthesis of molecularly imprinted polymers (MIPs) (synthetic antibodies) as soluble nanogels with sizes close to the size of real antibodies. To imprint a molecular memory in particles consisting of only a few polymer chains, an initiator carrying multiple iniferter moieties is used. This allows for the simultaneous initiation of several polymer chains, and yields molecularly imprinted nanogels (17 nm, molecular weight (MW) = 97 kDa) with good affinity and selectivity for the target.