Peptide conjugation to an in vitro-selected DNA ligand improves enzyme inhibition.
An in vitro selection technique was used to identify a specific high-affinity DNA ligand targeted to human neutrophil elastase (HNE). 1H 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.
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology; D009690:Nucleic Acid Conformation; D009698:Nucleoproteins / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011485:Protein Binding
D004791:Enzyme Inhibitors; D008024:Ligands; D009698:Nucleoproteins; D009842:Oligopeptides; D004247:DNA; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase