DNA–copper(II) complex and the DNA conformation

Abstract

Jlilirobioloyie und experimentelle Therapie der Deutschen Akademie der Synopsis Spectrophotometric, sedimentation, infrared, optical rotatory dispersion (Oltl)), and circxilar dichroisni (CI)) methods have beeti used to demonstrate the structural changes in DNA induced by the iiiteractioii of copper(I1) with bases and to elucidate the complex binding sites. As showii by the electrolyt,e-induced reversion (addit ion of salts) of temperat~ire-deriat~ired cwpper I ) S A the effectiveness of re-formation of the doublestranded structure depends o i l the temperature, copper(I1) ioii cwiiceiitration, and on the base compositioii of the I ) S A . ICxposure of heat-deliat tired c:.)pper I)NA to higher temperatures decreases the reversioii effert on addition of e1ec.t rolyte. The reilllts indicate that a greater frartioii with a c*ooperative transitioii appwrs o i i heating I>NA to 80 or 100°C at a Cii2+/l>?;A-P ratio of 2: 1 than at a Cii2+~I)XA-1' ratio of 1 : 1 . With AT-rich copper IIXA, reveixioii t o the iiaiive I ) S A striictiire wa-; i i o t observed. Selective methylatiori of griariiiie residiies i n I)XA also afl'ects the electrol?te-itiduced reversion, itidicatiiig the importance of GC pairs for copper(I1) binding aiid the reversion to the native structure. Temperature-deriat Ilred copper 1)XA shows an increased sedimentation coefficient which decreases again after electrolyte-iiidl1c.e 1 reversion. This change in s is reduced by selective methylatioii ( J f IINA. Chrnplex formation bet ween c:opper(II) and the bases is accompaiiied by a coiiformatioiial change of the I)NA double-helical striicliire as demonstrated by O I t I ) atid CI> experiments. The O l t l ) profile of GC-rich I)NA is murh more affected by copper(I1) than that of AT-rich ones. I*;ven at very low copper(I1) coricentr:ttio~rs, e.g., at O.W aiid 0.2 Ca2+/1)NA-P, the 0111) and CU measuremeiits exhibit cotiformat ioiial changes of the DNA secondary st rrictiire at room temperattire. By comparing the itifrared spectra of deoxytiiideosides with that. of I)NA of dift'ererit (;C content it has been shown t,hat both guanine and cyt.osirie are involved i n the formation of the complex of copper(I1) with IINA. N-7 and 0 at C-6 in guanine aiid N-3 as well as 0 of C-2 in cytosine are discussed as the most probable binding sites in I)NA. A binding model for the c:oorditiation of the copper(I1) ion between giiariine arid cytosine of the opposite >traiids is sriggested. The results are in good agreement with the assumptioris :uid predictions made by Kichhorn and Clark ahout the complexirig of copper(I1) with IINA. The recent proposal made by Schreiber aiid I):iriiie :tholit :tii ititerwtioii of the type g~i : i i i i t i e -~~i 2 + -g~~: i i i i i i e canriot. he exc*ltided :is an :idditioii:il kiiid of c~ooi~diii:itioii o f (*oppw(Il) i t 1 1)X.k.Various divaleiit metal ions are kno\vii to interact nit11 riucleic acids.L-LO Iri some investigations the results of metal determination in carefully isolated D S A preparations iiidicat e that certain metal io...

A Circular Dichroism Study of DNA . Platinum Complexes. Differentiation between Monofunctional. cis-Bidentate and trans-Bidentate Platinum Fixation on a Series of DNAs

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Catalytic Therapy of Cancer by Ascorbic Acid Involves Redox Cycling of Exogenous/Endogenous Copper Ions and Generation of Reactive Oxygen Species

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Structural Analysis of Cu Binding Site in [Cu(I)·d(CpG)·d(CpG)-2H]-1Complex

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