1995
DOI: 10.1073/pnas.92.24.11044
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Peptide conjugation to an in vitro-selected DNA ligand improves enzyme inhibition.

Abstract: An in vitro selection technique was used to identify a specific high-affinity DNA ligand targeted to human neutrophil elastase (HNE). 'H NMR data and a comparative analysis of the selected sequences suggest that the DNA folds into a G-quartet structure with duplexed ends. The highaffinity binding DNA

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Cited by 66 publications
(55 citation statements)
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“…Similar differences are also observed with cat G. DNA is another polyanion that reacts with NE. At physiological ionic strength, unfractionated DNA yield 25% inhibition of NE activity (29), whereas in vitro selected DNA sequences with high affinity for NE have no significant inhibitory effect on the enzyme (30). Tight enzyme-ligand binding with lack of inhibition might be explained by assuming ␣ ϭ 1 and ␤ ϭ 1, for instance (see Equation 3).…”
Section: Discussionmentioning
confidence: 99%
“…Similar differences are also observed with cat G. DNA is another polyanion that reacts with NE. At physiological ionic strength, unfractionated DNA yield 25% inhibition of NE activity (29), whereas in vitro selected DNA sequences with high affinity for NE have no significant inhibitory effect on the enzyme (30). Tight enzyme-ligand binding with lack of inhibition might be explained by assuming ␣ ϭ 1 and ␤ ϭ 1, for instance (see Equation 3).…”
Section: Discussionmentioning
confidence: 99%
“…Many other protein-binding aptamers have been proposed to form G-quadruplexes as part of their bioactive structure. [144][145][146][147][148] Although many proteins, including aptamers, oncogenic factors, [149a] antibodies, [150] and telomeric proteins, [12][13][14] all bind G-quadruplexes, there are few molecular details known about quadruplex-protein interactions. [12] The crystal structure of TBA bound to thrombin showed some ion pairs between the phosphate groups in the loops of the aptamer and Lys and Arg side chains.…”
Section: Molecular Recognition Of G-quadruplexes By Proteinsmentioning
confidence: 99%
“…However, one of the DNA aptamers were found to be able to modulate the reaction of human NE with the inhibitors secretory leukoprotease inhibitor (SLPI) and α 1 -proteinase inhibitor (α 1 -PI) (76). In an interesting construct made on the basis of these selections, a NE-binding DNA aptamer was covalently tethered to a tetrapeptide, which on its own weakly inhibited the enzymatic activity (K i ~1 mM) of human NE (75). The conjugate was able to completely inhibit human NE, with a K i of ~28 nM.…”
Section: General Properties Of Serine Proteases -mentioning
confidence: 99%
“…Several sets of aptamers binding to NE have been isolated, including a set of nuclease resistant RNA aptamers (74) and a set of DNA aptamers (75,76), in both cases with K D values in the low nanomolar range. Both sets of aptamers did not display measurable binding affinity to related proteins like thrombin, uPA, or porcine pancreatic elastase.…”
Section: General Properties Of Serine Proteases -mentioning
confidence: 99%