Oligoamine-acridine conjugates for promotion of gap-selective DNA hydrolysis by Ce(IV)/EDTA complex.
Oligoamines (spermidine, dipropylenetriamine and propylenediamine) were covalently attached to acridine via a hexamethylene linker. These oligoamine-acridine conjugates were efficiently bound to gap sites in substrate DNA, and promoted the DNA hydrolysis by a homogeneous Ce(IV)/ethylenediamine-N,N,N',N'-tetraacetate (EDTA) complex at these sites. In contrast, the hydrolysis of the double-stranded portion in the DNA was little affected by these conjugates, although they were strongly bound thereto by the intercalation of their acridine moieties. As a result, the gap site was selectively and efficiently hydrolyzed by combining the Ce(IV)/EDTA complex with the oligoamine--acridine conjugate. Either the oligoamine or the acridine was only poorly active for the purpose, substantiating the essential role of cooperation between them. The promotion of gap-selective DNA hydrolysis by the conjugates has been ascribed to electrostatic stabilization of a negatively charged transition state by their positive charges.
Yamamoto
Yoji
Y
Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
Tsuboi
Wataru
W
Komiyama
Makoto
M
D000166:Acridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002563:Cerium / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011073:Polyamines / Q000737:chemistry*; D011437:Propylamines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013057:Spectrum Analysis; D013095:Spermidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D055672:Static Electricity
D000166:Acridines; D004277:DNA, Single-Stranded; D046911:Macromolecular Substances; C476433:N-(6-chloro-2-methoxyacridin-9-yl)dipropylenetriamine; C476434:N-(6-chloro-2-methoxyacridin-9-yl)propylenetriamine; C476432:N-(6-chloro-2-methoxyacridin-9-yl)spermidine; D011073:Polyamines; D011437:Propylamines; D002563:Cerium; D004247:DNA; D004492:Edetic Acid; D013095:Spermidine