Macrocyclic zinc(II) complexes for selective recognition of nucleobases in single- and double-stranded polynucleotides |
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Authors: | E Kimura Takuya Ikeda Shin Aoki Mitsuhiko Shionoya |
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Institution: | (1) Department of Medicinal Chemistry, School of Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734, Japan Fax: +81-82-257-5234; e-mail: ekimura@ipc.hiroshima-u.ac.jp, JP;(2) Coordination Chemistry Laboratories, Institute for Molecular Science, Okazaki National Research Institutes, Nishigo-naka 38, Myodaiji, Okazaki 444, Japan Fax: +81-564-55-5245; e-mail: shionoya@ims.ac.jp, JP |
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Abstract: | As an extension of our earlier discoveries that ZnII-cyclen complex (1) (cyclen=1,4,7,10-tetraazacyclododecane) and ZnII-acridine-pendant cyclen complex ZnII-N-(9-acridin)ylmethyl-cyclen (3) are the first compounds to selectively recognize thymidine and uridine nucleosides in aqueous solution at physiological
pH, the interaction of these and a relevant complex, bis(ZnII-cyclen) (7), has been investigated with a series of polynucleotides, single-stranded poly(U) and poly(G), and double-stranded poly(A)·poly(U),
poly(dA)·poly(dT) and poly(dG)·poly(dC). These ZnII-cyclen complexes interact with the imide-containing nucleobases in the single-stranded poly(U), unperturbed by the presence
of the anionic phosphodiester backbone. The affinity constant of 1 for each N(3)-deprotonated uracil base in poly(U) is determined to be log K= 5.1 by a kinetic measurement, which is almost the same as log K=5.2 for the interaction of 1 with uridine. Thus, they disrupt the A-U (or A-T) hydrogen bonds to unzip the duplex of poly(A)·poly(U) or poly(dA)·poly(dT),
as demonstrated by lowering of the melting temperatures (T
m) of poly(A)·poly(U) and poly(dA)·poly(dT) in 5 mM Tris-HCl buffer (pH 7.6, 10 mM NaCl) with increase in their concentrations.
The order of the denaturing efficiency is well correlated with that of the 1 : 1 affinity constants for each complex with
uracil or thymine;7>3>1. The comparison of circular dichroism (CD) spectra for poly(A)·poly(U), poly(A), and poly(U) in the presence of 3 has revealed a structural change from poly(A)·poly(U) to two single strands, poly(A) and poly(U), caused by 3 binding exclusively to uracils in poly(U). On the other hand, the acridine-pendant cyclen complex 3, which earlier was found to associate with guanine by the ZnII coordinating with guanine N(7), in addition to the π-π stacking, interacts with guanine in the double helix of poly(dG)·poly(dC)
from outside and stabilized the double-stranded structure, as indicated by higher T
m.
Received: 31 December 1997 / Accepted: 23 February 1998 |
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Keywords: | Zinc complex Recognition of nucleobases Disruption of double-stranded DNA |
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