Interplay between Metal Ions and Nucleic Acids

388 Pages·2012·8.82 MB·English

by  Maria Pechlaner

Interplay between Metal Ions and Nucleic Acids
Metal Ions in Life Sciences
Volume 10
Series Editors:
Astrid Sigel, Helmut Sigel, and Roland K.O. Sigel
For further volumes:
http://www.springer.com/series/8385 and http://www.mils-series.com
Astrid Sigel (cid:129) Helmut Sigel (cid:129) Roland K.O. Sigel
Editors
Interplay between Metal
Ions and Nucleic Acids
Editors
Astrid Sigel Helmut Sigel
Department of Chemistry Department of Chemistry
Inorganic Chemistry Inorganic Chemistry
Universität Basel Universität Basel
Spitalstrasse 51 Spitalstrasse 51
CH-4056 Basel CH-4056 Basel
Switzerland Switzerland
[email protected] [email protected]
Roland K.O. Sigel
Institute of Inorganic Chemistry
Universität Zürich
Winterthurerstrasse 190
CH-8057 Zürich
Switzerland
[email protected]
The fi gure on the dust cover shows the upper part of Figure 2 (c) of Chapter 1 by M. Pechlaner
and Roland K. O. Sigel
ISSN 1559-0836 e-ISSN 1868-0402
ISBN 978-94-007-2171-5 e-ISBN 978-94-007-2172-2
DOI 10.1007/978-94-007-2172-2
Springer Dordrecht Heidelberg London New York
Library of Congress Control Number: 2011943624
© Springer Science+Business Media B.V. 2012
No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any
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Historical Development and Perspectives
of the Series
Metal Ions in Life Sciences*
It is an old wisdom that metals are indispensable for life. Indeed, several of them,
like sodium, potassium, and calcium, are easily discovered in living matter. However,
the role of metals and their impact on life remained largely hidden until inorganic
chemistry and coordination chemistry experienced a pronounced revival in the
1950s. The experimental and theoretical tools created in this period and their appli-
cation to biochemical problems led to the development of the fi eld or discipline now
known as B ioinorganic Chemistry , Inorganic Biochemistry , or more recently also
often addressed as Biological Inorganic Chemistry .
By 1970 B ioinorganic Chemistry was established and further promoted by the
book series Metal Ions in Biological Systems founded in 1973 (edited by H.S., who
was soon joined by A.S.) and published by Marcel Dekker, Inc., New York, for
more than 30 years. After this company ceased to be a family endeavor and its
acquisition by another company, we decided, after having edited 44 volumes of the
MIBS series (the last two together with R.K.O.S.) to launch a new and broader
minded series to cover today’s needs in the L ife Sciences . Therefore, the Sigels new
series is entitled
Metal Ions in Life Sciences .
After publication of the fi rst four volumes (2006–2008) with John Wiley & Sons,
Ltd., Chichester, UK, and the next fi ve volumes (2009–2011) with the Royal Society
of Chemistry, Cambridge, UK, we are happy to join forces now in this still new
endeavor with Springer Science & Business Media B.V., Dordrecht, The Netherlands;
a most experienced Publisher in the S ciences .
* Reproduced with some alterations by permission of John Wiley & Sons, Ltd., Chichester, UK
(copyright 2006) from pages v and vi of Volume 1 of the series Metal Ions in Life Sciences
(MILS-1).
v
vi Historical Development and Perspectives of the Series
The development of Biological Inorganic Chemistry during the past 40 years
was and still is driven by several factors; among these are (i) the attempts to reveal
the interplay between metal ions and peptides, nucleotides, hormones or vitamins,
etc., (ii) the efforts regarding the understanding of accumulation, transport, metabo-
lism and toxicity of metal ions, (iii) the development and application of metal-based
drugs, (iv) biomimetic syntheses with the aim to understand biological processes as
well as to create effi cient catalysts, (v) the determination of high-resolution struc-
tures of proteins, nucleic acids, and other biomolecules, (vi) the utilization of
powerful spectroscopic tools allowing studies of structures and dynamics, and
(vii), more recently, the widespread use of macromolecular engineering to create
new biologically relevant structures at will. All this and more is and will be refl ected
in the volumes of the series M etal Ions in Life Sciences .
The importance of metal ions to the vital functions of living organisms, hence, to
their health and well-being, is nowadays well accepted. However, in spite of all the
progress made, we are still only at the brink of understanding these processes.
Therefore, the series M etal Ions in Life Sciences will endeavor to link coordination
chemistry and biochemistry in their widest sense. Despite the evident expectation
that a great deal of future outstanding discoveries will be made in the interdiscipli-
nary areas of science, there are still “language” barriers between the historically
separate spheres of chemistry, biology, medicine, and physics. Thus, it is one of the
aims of this series to catalyze mutual “understanding”.
It is our hope that Metal Ions in Life Sciences proves a stimulus for new activities
in the fascinating “fi eld” of B iological Inorganic Chemistry . If so, it will well serve
its purpose and be a rewarding result for the efforts spent by the authors.
Astrid Sigel and Helmut Sigel
Department of Chemistry, Inorganic Chemistry,
University of Basel, CH-4056 Basel, Switzerland
Roland K.O. Sigel
Institute of Inorganic Chemistry,
Unversity of Zürich, CH-8057 Zürich, Switzerland
October 2005,
October 2008,
and August 2011
Preface to Volume 10

Interplay between Metal Ions and Nucleic Acids
The preceding Volume 9, S tructural and Catalytic Roles of Metal Ions in RNA , was
to a large part devoted to ribozymes, a vibrant but well defi ned research area. The
present volume, though related to the previous one, is of a much wider character
by describing phenomena that are generally due to the interrelations between metal
ions and nucleic acids, especially DNA. Yet it should be noted that the role of metal
ion-nucleic acid interactions in medication, tumor diagnosis, and anticancer
research is not specifi cally considered because these topics were dealt with in
Volumes 41 and 42 of our series M etal Ions in Biological Systems . Instead, Volume
10 focuses in 12 chapters on modern developments encompassing the wide range
from G-quadruplexes via DNAzymes to peptide nucleic acids (PNAs), topics of
relevance, e.g., for chemistry and nanotechnology, but also for molecular biology
and genetic diagnostics.
The volume opens with two general chapters. The fi rst one provides an overview
on metal ion-nucleic acid interactions and their characterization in solution by
describing the identifi cation of metal ion binding sites with chemical and biochemi-
cal methods, the application of NMR, etc. It deals with the determination of binding
constants and the effects of anions and buffers on metal ion binding to nucleic acids.
The corresponding interactions as seen in the solid state by crystal structure analysis
are the topic of Chapter 2. Though the interactions of metal ions with nucleic acids
and their constituents have attracted much attention over more than fi ve decades, the
review focuses mainly on results obtained during the past 15 years leading to tables
with over 200 entries. This large body of information is classifi ed and discussed.
Due to the fl exible nature of oligonucleotides, they can easily undergo conforma-
tional changes which may be observed by various methods. DNA can adopt a num-
ber of secondary structures of which the right-handed B-type helix is the predominant
form. The possible roles of metal ions regarding the transition from B- to A-DNA
(or Z-DNA), the transition from right- to left-handed helices, the denaturation of
double-strands, the condensation, and other conformational changes are discussed
vii
viii Preface to Volume 10
in Chapter 3. Special attention deserve polynucleotides containing long repeats of
guanosine nucleotides, which have long been known to have a marked tendency to
aggregate into gel-like materials as is pointed out in Chapter 4. Analysis has shown
that four strands are held together by a hydrogen bonding arrangement of four
guanines – the G-quartet. This very stable motif can self-associate and layers of
G-quartets may then be formed either from one, two or four strands of DNA or RNA
sequences. The roles of metal ions in stabilizing these four-stranded structures are
evaluated.
Living organisms from all kingdoms of life need transition metal ions as essen-
tial micronutrients as is emphasized in Chapter 5. On the other hand, the intrinsic
toxicity of the majority of these metal ions demands a tightly regulated intracellular
traffi cking that controls their concentration and minimizes the amount of free metal
ions. The crucial players in the metal homeostasis networks are specifi c metal-
responsive transcriptional regulators, generally defi ned as “metal sensors”; they
couple specifi c metal ion binding with a change in their DNA binding affi nity and/
or specifi city, thus translating the concentration of a certain metal ion into a change
in genetic expression.
Lanthanide(III) ions have been used as surrogates for alkaline earth ion binding
to nucleic acids. Indeed, as demonstrated in Chapter 6, detailed information about
the Ln(III) coordination sphere can be obtained from luminescence studies provid-
ing insights into metal ion-nucleic acid interactions. Similarly, certain metal ion
complexes are well known for their redox chemistry and their properties of oxygen
activation as pointed out in Chapter 7. DNA damage and cleavage by metal com-
plexes has attracted much attention since metal complexes may be useful tools for
studying molecular DNA lesions due to oxidative stress, which is implicated in
many disorders including aging, cancer, neurological diseases, etc. The review
focuses on examples illustrating fundamental mechanisms in the chemistry of DNA
oxidation by metal ion complexes.
For a long time DNA’s only function was perceived as being the genetic material
for all organisms. Because of the limitation of functional group diversity in the
building blocks of DNA and the mostly invariant double helical structure, DNA was
considered as being incapable of catalyzing chemical reactions. This contrasts with
the information assembled in Chapter 8: Nowadays we know that DNAzymes may
catalyze cleavage of RNA, the ligation of DNA and RNA, the formation of an RNA
branch or a lariat, as well as phosphorylation, adenylation, depurination of DNA,
and many more reactions. DNAzymes carry out their catalysis with the aid of metal
cofactors and some are very selective in this respect. Therefore, DNAzymes have
been converted into fl uorimetric, calorimetric, and electrochemical sensors for metal
ions. Furthermore, especially during the past two decades enantioselective catalysis
at the DNA scaffold has emerged, as reviewed in Chapter 9. Thus, DNA turned out
to be a highly versatile molecule for applications beyond its natural function, namely
in nanotechnology, DNA-templated synthesis, and hybrid catalytic systems.
The interior of the DNA duplex is formed by a parallel stack of pairwise-bonded
aromatic nucleobases. Hydrogen bonding, next to p -stacking and shape comple-
mentarity, plays an important role in governing the integrity of the double strand.
Preface to Volume 10 ix
Replacement of protons from the nucleobases by metal ions leads to base pairs in
which hydrogen bonds are formally replaced by coordinative bonds to metal ions.
As discussed in Chapter 10, artifi cial nucleotides have been developed with a large
affi nity towards metal ions. However, as shown in Chapter 11, metal-mediated base
pairs with natural nucleosides as well as artifi cial purine- or pyrimidine-derived
nucleosides may be used as well.
In the terminating Chapter 12 peptide nucleic acids (PNAs) are described; these
are non-cyclic pseudo-peptide-nucleic acid structural mimics, in which two nucleo-
bases are linked by a peptide unit instead of a ribosyl-phosphate-ribosyl unit.
Consequently, PNA binds more strongly to sequence complementary oligonucleo-
tides than does natural DNA or RNA because there is no electrostatic repulsion
between the strands. PNAs have caught the interest in many fi elds of science from
pure chemistry over molecular biology, drug discovery and (genetic) diagnostics to
nanotechnology and prebiotic chemistry. The review focuses on metal-complex
derivatives of PNA. Such derivatives offer the opportunity to introduce new labels
and probes for bioanalytical and diagnostic applications of PNA, but also to modulate
or to introduce, e.g., catalytic functions and to create specifi c biological activities.
Astrid Sigel
Helmut Sigel
Roland K.O. Sigel