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

An in vitro selection technique was used to identify a specific high-a ffinity DNA ligand targeted to human neutrophil elastase (HNE). H-1 NM R data and a comparative analysis of the selected sequences suggest th at the DNA folds into a G-quartet structure with duplexed ends. The hi gh-affinity binding DNA alone did not inhibit the enzymatic activity o f HNE. The DNA was covalently attached to a tetrapeptide, N-methoxysuc cinyl-Ala-Ala-Pro-Val, that is a weak competitive inhibitor of HNE. HN E was inhibited by this DNA-peptide conjugate nearly five orders of ma gnitude more effectively than by the peptide alone. These results demo nstrate that in vitro-selected nucleic acids can be used as a vehicle for molecular delivery.