PEPTIDE CONJUGATION TO AN IN VITRO-SELECTED DNA LIGAND IMPROVES ENZYME INHIBITION

摘要

An in vitro selection technique was used to identify a specific high-affinity DNA ligand targeted to human neutrophil elastase (HNE). H-1 NMR data and a comparative analysis of the selected sequences suggest that the DNA folds into a G-quartet structure with duplexed ends. The high-affinity binding DNA alone did not inhibit the enzymatic activity of HNE. The DNA was covalently attached to a tetrapeptide, N-methoxysuccinyl-Ala-Ala-Pro-Val, that is a weak competitive inhibitor of HNE. HNE was inhibited by this DNA-peptide conjugate nearly five orders of magnitude more effectively than by the peptide alone. These results demonstrate that in vitro-selected nucleic acids can be used as a vehicle for molecular delivery. [References: 38]