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Mechanistic studies of copper(II)-am...

Patwardhan, Anjali A.

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Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme./
Author:	Patwardhan, Anjali A.
Description:	106 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4933.
Contained By:	Dissertation Abstracts International64-10B.
Subject:	Chemistry, Inorganic. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3109096

Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme.
Patwardhan, Anjali A.

Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme. - 106 p.

Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4933.

Thesis (Ph.D.)--The Ohio State University, 2003.

The antibacterial activity of aminoglycosides stems from their high affinity binding to the 16S rRNA in bacteria resulting in inhibition of protein synthesis. Used to treat acute bacterial infections these antibiotics have limited applications due to their high dosage requirements and the emergence of resistant strains. We have synthesized and characterized Cu(II) derivatives of the aminoglycosides, kanamycin A, tobramycin, neamine, kanamycin B, neomycin B, and paromomycin. The first three exhibit preferential and tight binding to Cu(II) as against neomycin B and kanamycin B and paromomycin. EPR of frozen solutions and UV-visible spectroscopy suggest a change in geometry around the Cu(II) but the stabilities of the complexes in water differ. These copper derivatives efficiently cleave plasmid DNA at micromolar concentrations (hydrolytic) and at nanomolar concentrations in the presence co-reactants like hydrogen peroxide or ascorbic acid. Hydrolysis is multi turnover and exhibits Michelis-Menten kinetics with enzyme-like behavior whereas oxidative cleavage is highly specific propenal and nucleotide base products. Hydroxyl radicals generated are copper based and are generated in close proximity of the substrate.Subjects--Topical Terms:

517253
Chemistry, Inorganic.

Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme.
LDR:02777nmm 2200289 4500 001 1865323
005 20041217071845.5
008 130614s2003 eng d
035 $a (UnM)AAI3109096
035 $a AAI3109096
040 $a UnM $c UnM
100 1 $a Patwardhan, Anjali A. $3 1952775
245 1 0 $a Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme.
300 $a 106 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4933.
500 $a Adviser: James A. Cowan.
502 $a Thesis (Ph.D.)--The Ohio State University, 2003.
520 $a The antibacterial activity of aminoglycosides stems from their high affinity binding to the 16S rRNA in bacteria resulting in inhibition of protein synthesis. Used to treat acute bacterial infections these antibiotics have limited applications due to their high dosage requirements and the emergence of resistant strains. We have synthesized and characterized Cu(II) derivatives of the aminoglycosides, kanamycin A, tobramycin, neamine, kanamycin B, neomycin B, and paromomycin. The first three exhibit preferential and tight binding to Cu(II) as against neomycin B and kanamycin B and paromomycin. EPR of frozen solutions and UV-visible spectroscopy suggest a change in geometry around the Cu(II) but the stabilities of the complexes in water differ. These copper derivatives efficiently cleave plasmid DNA at micromolar concentrations (hydrolytic) and at nanomolar concentrations in the presence co-reactants like hydrogen peroxide or ascorbic acid. Hydrolysis is multi turnover and exhibits Michelis-Menten kinetics with enzyme-like behavior whereas oxidative cleavage is highly specific propenal and nucleotide base products. Hydroxyl radicals generated are copper based and are generated in close proximity of the substrate.
520 $a Hammerhead ribozymes are selectively hydrolyzed in the presence of divalent ions with Mg2+ being the metal ion of choice in vivo . Our studies with complex ions like cobalt hexaammine and fac-triamminetriaquochromium(III) establish outer sphere interactions of Mg2+ with the hammerhead in the catalytic site. There are two sets of sites, one structural and one catalytic. Complex ions in the catalytic site and divalent ions in the structural site result in a slow but active hammerhead ribozyme suggesting that the complex ions are not inhibitory, contrary to what was suggested previously.
590 $a School code: 0168.
650 4 $a Chemistry, Inorganic. $3 517253
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Engineering, Materials Science. $3 1017759
690 $a 0488
690 $a 0487
690 $a 0794
710 2 0 $a The Ohio State University. $3 718944
773 0 $t Dissertation Abstracts International $g 64-10B.
790 1 0 $a Cowan, James A., $e advisor
790 $a 0168
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3109096