Nucleoside Triphosphates and their Analogs: Chemistry, Biotechnology, and Biological Applications

408 Pages·2005·7.14 MB·English

by  Morteza Vaghefi (Editor)

Nucleoside
Triphosphates
Analogs
and their
Chemistry, Biotechnology,
and
Biological Applications
Morteza Vaghefi

Nucleoside
Triphosphates
Analogs
and their
Chemistry, Biotechnology,
and
Biological Applications
Published in 2005 by
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 2005 by Taylor & Francis Group, LLC
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International Standard Book Number-10: 1-57444-498-0 (Hardcover)
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Library of Congress Cataloging-in-Publication Data
Nucleoside triphosphates and their analogs : chemistry, biotechnology, and biological applications /
edited by Morteza M. Vaghefi.
p. cm.
Includes bibliographical references and index.
ISBN 1-57444-498-0 (alk. paper)
1. Nucleotides. 2. Nucleotides—Derivatives. 3. Adenosine triphosphate. I. Monir-Vaghefi, Seyed-
Morteza. II. Title.
QP625.N89N838 2005
611'.01816—dc22 2004065509
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The Editor
Morteza M. Vaghefi, Ph.D., received his graduate training at the University
of Utah and Brigham Young University in Utah, obtaining an M.S. degree
(1980) in biochemistry and a Ph.D. (1985) in organic and medicinal chemistry
under the guidance of Professor Ronald Robins. Dr. Vaghefi is an inventor
of eight patents and has authored over 30 scientific publications. He is
currently serving as the reviewer for the Journal of Medicinal Chemistry and
Nucleosides, Nucleotides and Nucleic Acid.
From 1985 to 1989, Dr. Vaghefi served as head of the Department of
Biomedicinal Chemistry at ICN Pharmaceuticals Inc., developing novel
nucleoside and nucleotide analogs for various therapeutic indications. In
1989, he accepted a position at Genta Inc. in San Diego, California, serving
as the head of oligonucleotides and nucleotide chemistry. In 1996, he
cofounded TriLink Biotechnologies Inc. in San Diego.
From 1996 to 2004, Dr. Vaghefi served as cofounder and senior vice
president and chief chemical officer of TriLink Biotechnologies Inc., which
is involved in the research and synthesis of novel, labeled nucleotide, nucle-
oside, and oligonucleotides. Dr. Vaghefi currently serves as founder and
president of a San Diego-based start-up company, ChemCyte Corporation.
His current research interests include, labeled nucleotide triphosphate as a
tool for diagnostics; oligonucleotide labeling technology; novel nucleoside
drug target discovery; nucleic acids as targets for small molecule interven-
tion; and fluorescent labeling.

Contributors
Wissam Abdel–Gawad Kevin A. Fiala
The Biophysics Program and Department of Biochemistry
Department of Biochemistry The Ohio State University
The Ohio State University Columbus, Ohio
Columbus, Ohio
Ikuhide Fujisawa
Katsuyuki Aoki
Department of Materials Science
Department of Materials Science
Toyohashi University of
Toyohashi University of
Technology, Tempaku-cho
Technology, Tempaku-cho
Toyohashi 441-8580, Japan
Toyohashi 441-8580, Japan
Phillip A. Furman
Veeraiah Bodepudi
Pharmasset, Inc.
Department of Core Chemistry
Tucker, Georgia
Roche Molecular Diagnostics
Alameda, California
Allison A. Johnson
Erik De Clercq Laboratory of Molecular
Rega Institute for Medical Research Pharmacology, NCI, NIH
B-3000 Leuven, Belgium Bethesda, Maryland
Staffan Eriksson
Inna Koukhareva
Department of Molecular
Trilink Biotechnologies Inc.
Biosciences, Section of Veterinary
San Diego, California
Medical Biochemistry
Swedish University of Agricultural
Alexandre Lebedev
Sciences
Trilink Biotechnologies Inc.
The Biomedical Center
San Diego, California
Uppsala, Sweden
Joy Y. Feng Glenn H. McGall
Gilead Sciences Affymetrix
Durham, North Carolina Santa Clara, California
Zucai Suo Louise Wang
Department of Biochemistry Institute of Cellular and Molecular
The Ohio State University Biology
Columbus, Ohio University of Texas at Austin, Texas
Seng-Lai Tan Stephen G. Will
Lilly Research Laboratories Department of Core Chemistry
Eli Lilly & Company Roche Molecular Diagnostics
Indianapolis, Indiana Alameda, California
Morteza Vaghefi
ChemCyte Corporation
San Diego, California
Introduction
The first nucleoside triphosphate (NTP), adenosine triphosphate (ATP), was
discovered by Karl Lohmann in 1929. Some years later, its structure was
clarified, and Alexander Todd synthesized ATP chemically in 1948. A major
role of ATP is supplying the needed energy to synthesize the many thousands
of macromolecules that a cell needs to exist. ATP is described as the “uni-
versal currency of energy” in the cell and functions as a carrier of energy in
all living organisms from bacteria and fungi to plants and animals, including
humans. The actual power source is the phosphate tail of ATP. Available
energy is contained in the bonds between the phosphates and is released
when they are hydrolyzed. Usually, only the outer phosphate is removed to
yield energy and the nucleotide diphosphate. Although ATP is the main
energy carrier in the cell, other energized nucleotides containing thymine,
guanine, uracil, and cytosine are utilized. Nucleoside diphosphate kinase
transfers energy contained in a nucleoside triphosphate (commonly ATP) to
a nucleoside diphosphate, such as guanosine diphosphate (GDP), to form
guanosine triphosphate (GTP).
Nucleoside triphosphates are utilized by a family of polymerases during
the synthesis of nucleic acids on preexisting nucleic acid templates, assem-
bling RNA from ribonucleotides, or DNA from deoxyribonucleotides. Poly-
merase chain reaction (PCR), a key technique in molecular genetics that
permits the analysis of any short sequence of DNA (or RNA) in the test tube,
relies on NTP. The PCR technology has greatly increased scientists’ ability
to study genetic material. Since its invention, PCR has revolutionized the
way in which basic research and medical diagnosis are conducted.
Structurally, NTP consists of three main components: the nitrogenous
base, the sugar, and a chain of three phosphate groups bound to ribose. Since
the discovery of the first nucleotide and elucidation of its structure (ATP),
scientists have synthesized various analogs of NTP modified at the base,
sugar, or triphosphate chain. These compounds have served as valuable tools
in the investigation of a variety of cellular processes for many years. Mod-
ification of the triphosphate chain has been mainly used to study enzymatic
pathways, which results in hydrolysis or transfer of the phosphate from NTP
to another molecule. Modification of sugar and base has served a number
of different purposes, from pharmaceutical to diagnostic applications.