Aminoglycoside Antibiotics: From Chemical Biology to Drug Discovery

339 Pages·2007·9.54 MB·English

by  Dev P. Arya

AMINOGLYCOSIDE
ANTIBIOTICS

AMINOGLYCOSIDE
ANTIBIOTICS
From Chemical Biology to Drug Discovery
DEV P. ARYA
Clemson University
WILEY-INTERSCIENCE
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CONTENTS
Preface vii
Contributors ix
1. In the Beginning There Was Streptomycin 1
JulianDavies
2. The Biochemistry and Genetics of Aminoglycoside Producers 15
WolfgangPiepersberg,KhaledM.Aboshanab,HeikeSchmidt-Beißner,
andUdoF.Wehmeier
3. Mechanisms of Aminoglycoside Antibiotic Resistance 119
TusharShakyaandGerardD.Wright
4. Design, Chemical Synthesis, and Antibacterial Activity
of Kanamycin and Neomycin Class Aminoglycoside
Antibiotics 141
JinhuaWangandCheng-WeiTomChang
5. NMR Structural Studies of Aminoglycoside:
RNA Interaction 181
R.AndrewMarshallandJosephD.Puglisi
v
vi CONTENTS
6. Structural Comparisons Between Prokaryotic and Eukaryotic
Ribosomal Decoding A Sites Free and Complexed with
Aminoglycosides 209
JiroKondoandEricWesthof
7. Binding of Antibiotics to the Aminoacyl-tRNA Site of Bacterial
Ribosome 225
DaleKling,ChristineChow,andShahriarMobashery
8. Metalloaminoglycosides: Chemistry and Biological Relevance 235
NikhilGokhale,AnjaliPatwardhan,andJ.A.Cowan
9. Adverse Effects of Aminoglycoside Therapy 255
AndraE.TalaskaandJochenSchacht
10. Targeting HIV-1 RNA with Aminoglycoside Antibiotics and
Their Derivatives 267
LevElson-SchwabandYitzhakTor
11. Novel Targets for Aminoglycosides 289
DevP.Arya,NicholasShaw,andHongjuanXi
Index 315
PREFACE
Since Selman Waksman’s discovery of streptomycin in 1944, aminoglycosides
have been at the forefront of antibacterial drug treatment. Advances in carbohy-
drate chemistry and biochemistry, coupled with other technological advances in
nucleic acidsynthesis, biochemistry andstructure analysis have ledto a substan-
tial increase in aminoglycoside research among both chemists and biochemists.
While by no means exhaustive, this endeavor attempts to chronicle the advances
made in aminoglycoside-related work over the last two decades to assist new
researchers in the field of aminoglycoside research while also offering a refer-
ence guide for the expert. Any omission of work is unintentional and due partly
to the time constraints always present in such a venture.
Intheintroduction,Dr.Davies’narrativeofaminoglycosideresearchprovides
us with an elegant historical perspective on aminoglycoside discovery and the
mechanism of action over the past 50 years. Chapter 2 illustrates the progress
made in the elucidation of the biosynthetic pathways for aminoglycoside syn-
thesis. Piepersburg and coworkers have outlined the major pathways and their
work should serve as an important reference guide for years to come. A major
probleminaminoglycosidetherapyhasbeendrugresistanceandinChapter 3are
thefindingsofShakyaandWrightregardingtheirarticulationofthemajormech-
anisms of aminoglycoside resistance and the possible methods for overcoming
these pathways. To get past the resistance mechanisms, chemistry and biology
must come together and in Chapter 4, Wang and Chang summarize the synthetic
advances made in aminoglycoside chemistry over the past decade and their uses
in the development of improved antibiotics.
A large interest among chemists and biochemists in aminoglycosides stems
also from the fact that their molecular RNA target of therapeutic action has
been identified. Chapters 5–7 provide a broad overview of the interaction of
vii
viii PREFACE
aminoglycoside with RNA focusing particularly on the A-site, their ribosomal
target. In Chapter 5, Marshall and Puglisi first summarize the advances made in
theNMR-basedstructuralinvestigationofaminoglycosideswithRNA,including
the A-site. In Chapter 6, Kondo and Westhof detail the progress made in the
crystallographic investigations of RNA–aminoglycoside interactions and how
thathasbeenusedtodecipherthedifferencesbetweeneukaryoticandprokaryotic
ribosomal drug targets. Kling, Chow and Mobashery summarize the different
approaches regarding the further comprehension of this important nucleic-acid
interaction. Together, these accountsshould provide an excellentreferenceguide
for students and established researchersinterested in the field of aminoglycoside
biochemistry, biophysics, chemical biology or medicinal chemistry.
In Chapter 8, Cowan and coworkers review the state of the art on the metal-
mediatedaminoglycosideresearchresultinginpossiblemetallozymesthatcanbe
developed as novel drugs and tools for DNA and RNA cleavage. A major issue
preventingthedevelopmentofaminoglycosidetherapieshastodowiththeirtox-
icity.Asthemechanismscausingtheseaminoglycosidetoxicities(ototoxicityand
nephrotoxicity) become clearer, molecular mechanisms to circumvent the propa-
gation of these toxicities are being proposed. Talaska and Schacht discuss these
proposedmechanismsandthepossibleroleofiron-mediatedfreeradicaldamage
leading to oxidative stress. For other molecular mechanisms in the genetic basis
of aminoglycoside ototoxicity, the reader is advised to consult the references at
the end of Chapter 1. In Chapter 10, Elson-Schwab and Tor describe the use of
aminoglycosides in other medicinally relevant RNA targets, specifically those
involved in HIV therapy. The work elegantly illustrates how the congruence of
chemistryandbiologycanleadtonovelparadigmsindrugdevelopment.Finally,
Arya and coworkers summarize the recent work in some non-RNA targets dis-
covered for aminoglycoside-based recognition and how chemical manipulations
can be used to tailor aminoglycoside specificities.
Aminoglycoside research is now a legitimate aspect of scientific endeavor;
with much knowledge, yet unknown, that we can learn. Aminoglycosides have
broughttogetheranumberofdifferentdisciplines(andmanymoredisciplinesare
expectedtobepositivelyaffectedbyaminoglycosideresearch).Itismyhopethat
thisbookwillassistinboththecontinuingprogressandexpansionofaminoglyco-
sideresearchintodrugdevelopment,chemicalbiology,biophysics,microbiology,
toxicology,molecularrecognitionandcarbohydratechemistry.I wishtothankall
the authors for their wholehearted collaboration in this endeavor. Without them
this book would not have been possible.
DevPriyaArya
Clemson
CONTRIBUTORS
KhaledM.Aboshanab, BUWuppertal,ChemicalMicrobiology,D-42097Wup-
pertal, Germany
Dev P. Arya, Laboratory of Medicinal Chemistry, Department of Chemistry,
Clemson University, Clemson, SC 29634
Cheng-Wei Tom Chang, Department of Chemistry and Biochemistry, Utah
State University, Logan, UT 84322
ChristineChow, DepartmentofChemistry,WayneStateUniversity,Detroit,MI
48202
J. A. Cowan, Department of Chemistry, Ohio State University, Columbus, OH
43210
Julian Davies, Department of Microbiology and Immunology, University of
British Columbia1 Life Sciences Institute,2 Vancouver BC V6T 1Z3, Canada
Lev Elson-Schwab, Department of Chemistry and Biochemistry, University of
California, San Diego, La Jolla, CA 92093
Nikhil Gokhale, Department of Chemistry, Ohio State University, Columbus,
OH 43210
Dale Kling, Department of Chemistry and Biochemistry, University of Notre
Dame, Notre Dame, IN 46556
Jiro Kondo, Institut de Biologie Mole´culaire et Cellulaire, UPR9002 CNRS,
Universite´ Louis Pasteur, 67084 Strasbourg, France
R. Andrew Marshall, Department of Chemistry, Stanford University, Stanford,
CA 94305
Shahriar Mobashery, Department of Chemistry and Biochemistry, University
of Notre Dame, Notre Dame, IN 46556
ix