Introduction to bioorganic chemistry and chemical biology:
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York ; London
Garland Science, Taylor & Francis Group
[2013]
Boca Raton ; London ; New York CRC Press, Taylor & Francis Group |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XVII, 486 S. Ill. |
| ISBN: | 9780815342144 0815342144 |
Internformat
MARC
| LEADER | 00000nam a2200000zc 4500 | ||
|---|---|---|---|
| 001 | BV040908358 | ||
| 003 | DE-604 | ||
| 005 | 20211124 | ||
| 007 | t | ||
| 008 | 130325s2013 a||| |||| 00||| eng d | ||
| 020 | |a 9780815342144 |c (pbk.) £48.00 |9 978-0-8153-4214-4 | ||
| 020 | |a 0815342144 |c (pbk.) £48.00 |9 0-8153-4214-4 | ||
| 035 | |a (OCoLC)844040388 | ||
| 035 | |a (DE-599)OBVAC10721116 | ||
| 040 | |a DE-604 |b ger | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-91G |a DE-355 |a DE-19 |a DE-20 |a DE-83 | ||
| 082 | 0 | |a 572 | |
| 084 | |a VK 8500 |0 (DE-625)147535:253 |2 rvk | ||
| 084 | |a WD 5000 |0 (DE-625)148184: |2 rvk | ||
| 084 | |a CHE 800f |2 stub | ||
| 100 | 1 | |a Van Vranken, David L. |e Verfasser |0 (DE-588)1030300488 |4 aut | |
| 245 | 1 | 0 | |a Introduction to bioorganic chemistry and chemical biology |c David Van Vranken and Gregory Weiss |
| 264 | 1 | |a New York ; London |b Garland Science, Taylor & Francis Group |c [2013] | |
| 264 | 1 | |a Boca Raton ; London ; New York |b CRC Press, Taylor & Francis Group | |
| 264 | 4 | |c © 2013 | |
| 300 | |a XVII, 486 S. |b Ill. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 0 | 7 | |a Chemische Biologie |0 (DE-588)7657972-4 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Naturstoffchemie |0 (DE-588)4171332-1 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Biochemie |0 (DE-588)4006777-4 |2 gnd |9 rswk-swf |
| 653 | |a Biochemistry. | ||
| 689 | 0 | 0 | |a Biochemie |0 (DE-588)4006777-4 |D s |
| 689 | 0 | 1 | |a Naturstoffchemie |0 (DE-588)4171332-1 |D s |
| 689 | 0 | 2 | |a Chemische Biologie |0 (DE-588)7657972-4 |D s |
| 689 | 0 | |C b |5 DE-604 | |
| 700 | 1 | |a Weiss, Gregory A. |e Verfasser |0 (DE-588)1030301530 |4 aut | |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025887737&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-025887737 | ||
Datensatz im Suchindex
| _version_ | 1804150193615011840 |
|---|---|
| adam_text | Titel: Introduction to bioorganic chemistry and chemical biology
Autor: Van Vranken, David L
Jahr: 2013
Contents
Chapter 1 The Fundamentals of Chemical Biology 1
Chapter 2 The Chemical Origins of Biology 27
Chapter 3 DNA 57
Chapter 4 RNA 131
Chapters Peptide and Protein Structure 179
Chapter 6 Protein Function 229
Chapter 7 Glycobiology 281
Chapter 8 Polyketides and Terpenes 339
Chapter 9 Chemical Control of Signal Transduction 397
Glossary 461
Index 469
Detailed Contents
Chapter 1 1.6 SOME COMMON TOOLS OF CHEMICAL BIOLOGY 15
The Fundamentals of Chemical Biology 1 Chromophores reveal invisible molecules 15
Why organize a book on chemical biology around Assays COnnect moleCular entitieS t0 readi y ViSib e . 6
biooligomers? 1 D phen°mena , . , .. , t. ™
Powerful microbiological screens reveal interesting
1.1 THE CENTRAL DOGMA OF MOLECULAR BIOLOGY 2 chemical phenomena
The central dogma of molecular biology is an
17
Viruses deliver genes efficiently 18
transcriptome 10
RJSS^r?JI^/Pn^am^ .« 2.1 MECHANIC ARROW-PUSHING .SAN
the diversity of the proteome 10
19
organizing principle for chemical biology 2 Vast libraries of proteins can be screened in vitro
using bacteriophages
i.z utiNts 3 screens of DNA and RNA push the limits
A gene is made up of a promoter and a transcribed ,... .. . 19
sequence 3 Small molecules take control 19
1.3 GENOMES 5 Short RNA molecules silence gene expression 21
We have sequenced the human genome and many Monoclonal antibodies bind specifically 21
others. Now what? 5 Immortal cancer cell lines serve as mimics of human
We are far from understanding cells that we understand organs 21
the best-Escherichia coli 5 Human stem cells are highly valuable tools for
We are even farther from understanding human cells 6 research and medicine 22
You cannot judge a cell by its genome 8 Model organisms teach us about humans 22
The observable phenotype belies the hidden genotype 9 summary 24
1.4 SOURCES OF DIVERSITY BEYOND GENOMES 9 25
The transcriptome is the collection of all of the RNA PROBLEMS
transcripts in a cell 9
RNA splicing amplifies the diversity of the Chapter 2
The Chemical Origins of Biology 27
EXPRESSION OF MOLECULAR ORBITAL THEORY 27
Beyond template-directed synthesis of biooligomers 11 £™C» N ^ ^v-ul** wi™ , n, . ™.w .
Three properties control chemical reactivity *¦
1.5 COMBINATORIAL ASSEMBLY GENERATES Perturbational molecular orbital theory connects
DIVERSITY 12 arrow-pushing with quantum mechanics 28
Combinatorial assembly of linear biooligomers can Six canonical frontier orbitals can be used to predict
generate massive diversity 12 reactivity 29
Combinatorial synthesis can be used to synthesize Electronegativity affects both frontier orbitals and
DNA libraries 13 Coulombic interactions 31
Modular architecture lends itself to the synthesis of Curved mechanistic arrows depict the interaction
non-natural chemicallibraries 13 of filled orbitals with unfilled orbitals 32
The human immune system uses combinatorial There are three basic rules for mechanistic arrow-
btosynthes.s 14 pgshing 32
DETAILED CONTENTS xf
2.2 HYDROGEN BONDS AND PROTON TRANSFERS 33 3.2 THE RIBONUCLEOTIDE SUBUNITS OF DNA 59
Hydrogen bonds involve three atoms 33 Nucleotides are phosphate esters 59
Proton transfers to and from heteroatoms are usually DNA and RNA are polymers of nucleotides 60
very fast 34 Are the heterocyclic DNA bases aromatic? 60
Linear geometries are preferred for proton transfers 35 Nucleic acids are not acidic, and DNA bases are not
basic 62
2.3 PREBIOTIC CHEMISTRY 36 T. . . .,,. . . ,~MA ,
,,_,, , .~ ¦ . . . The missing 2 -hydroxyl group of DNA confers
HCN and CH20 are key ingredients in the primordial stabi|jty tQ phosphodiester hydro|ysis 62
soup 36
Modifications to DNA bases are as important as the
Solutions of HCN contain both nucleophile and nucleotide DNA sequence 63
electrophile at pH 9.2 37
HCN forms purines and pyrimidines under prebiotic 3-3 ELEMENTARY FORCES IN DNA 64
conditions 38 Base pairing knits together the two strands of DNA 64
Aldol reactions with formaldehyde generate Some non-natural, isomeric bases form effective
carbohydrates 40 base pairs 66
Cyanide catalyzes the benzoin reaction 40 Hydrogen bonds are not absolutely essential for
Did we arise from a primordial RNA world? 41 complementary base pairing 67
Amino acids arise spontaneously under prebiotic Hoogsteen base pairing is present in triplex DNA 68
conditions 41 Aromatic n stacking stabilizes the DNA double helix 68
Intercalation between DNA base pairs involves n
2.4 NONBONDING INTERACTIONS 42 stacking 69
Essentially everything taking place in the cell involves Double-stranded DNA undergoes reversible unfolding
nonbonding interactions 42 and refolding 69
The weak energies of nonbonding interactions are Complementarity drives self-assembly of DNA 71
not easily calculated using perturbational molecular short stretches of DNA can fold into hairpins 72
orbital theory 43
. .. y . , t. .. . . 3.4 DNA SUPERSTRUCTURE 73
For nonbonding interactions, the energies can be
fitted to a simplified equation 43 Double-stranded DNA forms supercoils 73
van der Waals interactions can be described by the Topoisomerases resolve topological problems with
DNA 73
Lennard-Jones potential 44
It is helpful to distinguish reversible from irreversible
Bacterial plasmids are rings of DNA 74
interactions 45 Plasmids contain genes that confer advantageous
traits 75
Eukaryotic DNA is coiled around histone proteins 76
Entropy makes it difficult to identify favorable states
among seemingly endless possibilities 47
The hydrophobic effect results from a balance 3.5 THE BIOLOGICAL SYNTHESIS OF DNA BY
between attractive forces and entropy 47 POLYMERASE ENZYMES 78
____, _,.1^1.1 DNA polymerases lengthen existing strands 78
2.5 THE POWER OF MODULAR DESGN 48 .. , s -.uu-uej.-.
..,,,. , DNA polymerases copy with high fidelity 79
Modular design underlies the five basic types of Reverse transcriptase ,engthens existing DNA strands
biooligomers 48 0n an RNA template 79
Labihty correates inverse y with information ongevity 49 _.,... , . ^ .., . . ... ..
,° J . ._,,,. DNA polymerase incorporates modified thymidylate
Why are esters more reactive than amides? 50 residues 80
Why are phosphate esters less reactive than _ . __ , . . .., _klA
-Li^wT,!^ Jltorc? ci The polymerase chain reaction amplifies DNA
through iterative doubling 81
3.6 THE CHEMICAL SYNTHESIS OF DNA 82
PROBLEMS 54 The race to crack the genetic code drove the
development of DNA synthesis 82
Chapter 3 Tne Khorana method of DNA synthesis relies on
r »i/k 57 phosphate coupling chemistry 83
Letsinger recognized the speed and efficiency of
3.1 FORMS OF DNA 57 phosphite couplings 83
The canonical double helix is one of several forms Caruthers synthesized DNA by using phosphoramidites
of DNA 57 on solid phase 84
The organization of genomic DNA molecules Automated oligonucleotide synthesis is performed
depends on the type of organism 58 on glass particles 85
carboxylic esters? 51
2.6 SUMMARY 53
SHU:
Modern automated DNA synthesis involves repetitive DNA is a nucleophile 110
four-step cycles 86 Simple alkylating agents are highly mutagenic 110
The 4,4 -dimethoxytrityl group is deprotected through Bifunctional alkylating agents that crosslink DNA are
an SN1 reaction 86 highly cytotoxic 111
Tetrazole serves as an acid catalyst in phosphoramidite Strained rings can bring highly reactive functional
couplings 87 groups to DNA 112
Capping unreacted 5 -hydroxyl groups prevents the Epoxide alkylators of DNA are highly mutagenic 113
propagation of mistakes 87 Aziridinium rings are relatively selective alkylators
Oxidation of unstable phosphites generates stable of DNA H4
phosphates 88 Cyclopropane rings can serve as spring-loaded
Aqueous ammonium hydroxide cleaves and electrophiles 115
deprotects synthetic DNA 89 Free radicals and oxygen conspire to cleave DNA
Microarrays of DNA facilitate screening 89 sugars I17
Why are DNA and RNA made up of five-membered Enediyne antitumor antibiotics cleave both strands
ring sugars? 90 of DNAviapora-benzynediradicals 118
3.7 SEPARATE OF DNA MOLECULES BY Some highly reactive enediyne natural products are
ELECTROPHORESIS 91 protected by protein delivery veh.cles 122
* ; j. . ¦. • *u •? : Bleomycin catalyzes the formation of reactive
Scientists use different criteria for the purity of . 123
biological macromolecules versus small, organic ° y^
molecules 91 3.11 SUMMARY 124
Agarose gel is used for electrophoresis of long DNA prori EMS 125
molecules 92
Capillary electrophoresis is used for analytical Chapter 4
separation of short DNA molecules 94 RN- «¦*]
DNA dideoxy sequencing capitalizes on the
tolerance of DNA polymerase 95 4.1 RNA STRUCTURE 132
Large-scale sequencing methods avoid the need The nucleotide subunits of RNA are subtly different
for electrophoresis 96 from those of DNA 132
3.8 RECOMBINANT DNA TECHNOLOGY 97 The 2 -OH of RNA confers high chemical reactivity 132
Molecular biology connects DNA molecules to Ubiquitous ribonucleases rapidly degrade RNA 133
biological phenotypes 97 The s-™e^y group of thymine is a form of chemical
Restriction endonudeases cut DNA at specific sites ID , ,
and facilitate re-ligation 98 RNA adopts 9 obular shapes because it is single-
Mutations in DNA can lead to changes in expressed stranded 135
Proteins 101 4.2 RNA SYNTHESIS 139
Site-directed mutagenesis involves labile plasmid RNA polymerases create new strands of RNA 139
templates 102 DNA primase is just another RNA polymerase 140
3.9 NUCLEIC ACID PHOTOCHEMISTRY 102 4.3 TRANSCRIPTIONAL CONTROL 141
Ultraviolet radiation promotes [2+2] photodimerization DNA sequences determine start sites and stop sites
of thymine and uracil bases 102 for RNA polymerase 141
Thymine dimers in DNA can be repaired 103 Transcription factors bind to DNA with exquisite
Psoralens intercalate between DNA base pairs and sequence specificity 142
photocrosslink opposing strands 104 Transcription can be controlled by small molecules 143
3.10 DNA AS A TARGET FOR CYTOTOXIC DRUGS 105 Transcription of mRNA in human cells involves many
Cell division is highly controlled in normal human proteins and many regions of DNA 145
cells •! q5 The yeast two-hybrid system provides a transcription-
Dividing human cells must pass through checkpoints, Dased t00 to identify protein-protein interactions 146
Tr^lSL. u *u 105 4A mRNAPROCESSING IN EUKARYOTES 148
dtS.ll? Py tar9etS °NA in rapidly After sy thesis eukary°t* onanisms modify their
.nhhlTf L CanCerS°rr0t m mRNA extensively 148
^t£^!rZK^i,,,^ 107 ^^-^HemRNAarecappedandpo.yadeny.ated 149
Adding the methyl group to?Se is essential ?°* ^S?0* ^ ^ ^ mRNA spBdn9 5°
for DNA synthesis essential Some RNA introns undergo self-splicing without a
y 108 spliceosome 151
DETAILED CONTENTS xlll
4.5 CONTROLLED DEGRADATION OF RNA 152 Chemical peptide synthesis involves repeated
Ribonuclease H degrades RNA DNA duplexes 152 additions of activated carboxylates to the N terminus 188
RNA-induced silencing complexes target specific The need to remove excess reagents and chemical
mRNA sequences 153 by-products drove the development of solid-phase
RNA interference is a useful laboratory tool 155 peptide synthesis 188
4.6 RIBOSOMALTRANSLATION OF mRNA Eitl?er acid or base labile carbamates are used for
INTO PROTEIN 156 the temporary protection of the Na group 189
T. .. . .. . . , Carbodiimides drive condensation to form peptide
The nbosome catalyzes ohgomenzation of a-ammo , , ion
esters 156
The ribosome is a massive molecular machine, half
protein and half RNA 157
Side reactions can compete with peptide coupling
reactions 190
HOBt minimizes side reactions in carbodiimide
tRNA molecules are heavily processed and adopt fixed couolinqs 191
shapes 159 Uranium coupling agents provide even faster
The genetic code allows one to translate from mRNA amide bond formation 192
sequence into protein sequence 161 Resins for solid-phase peptide synthesis are made
tRNA synthetases recognize amino acids and of plastic 193
nucleotides 162 Cleavable linkers between the synthesized peptide
What controls the beginning and end of translation? 163 and solid support provide stable, yet reversible,
Translational initiation is a focal point for control of attachments 193
protein synthesis 165 Side-chain protecting groups come off under
A protein escorts each aminoacyl-tRNA to the acidic conditions 195
ribosome for fidelity testing 166 Peptide nucleic acids lack phosphate esters and
The genetic code can be expanded beyond 20 amino ribofuranose rings 196
acjds 167 Native chemical ligation generates cysteinyl amides
Ligand-dependent riboswitches control protein through aminolysis of thiol esters 197
expression 169 5.3 FUNDAMENTAL FORCES THAT CONTROL
Many antibiotics target bacterial protein synthesis 170 PROTEIN SECONDARY STRUCTURE 199
4.7 FROM OLIGONUCLEOTIDE LIBRARIES TO Secondary structure involves different patterns of
PROTEIN LIBRARIES 171 hydrogen bonding between backbone amides 199
Automated oligonucleotide synthesis facilitates a Hejices allow effective hydrogen bonding between
generation of both DNA and RNA oligonucleotide
neighboring amide N-H and C=0 200
libraries 171 ^ Sheets satisfy hydrogen bonding by backbone
RNA libraries can be screened for ribozymes 173 amides with linkages between different strands 201
mRNA libraries can be expressed as protein libraries 174 Turn structures have minimal hydrogen bonding
between backbone amides 202
4.8 SUMMARY 175 Rotation about substituted ethanes, butanes, and
PROBLEMS 176 pentanes reveals the fundamental forces dictating
protein folding 203
Chapter 5 Stereoelectronic effects distinguish amides and
Peptide and Protein Structure 179 esters from substituted ethenes 204
r Interactions between allylic substituents and alkene
5.1 AMINO ACIDS AND PEPTIDES 180 substituents limit the conformation of substituted
The standard ribosomal amino acids include a broad propenes 205
range of functionalities 180 Allylic strain explains the dominance of two types
Amino acids are polymerized into peptides and of secondary structures 206
Proteins , .. t . . ,. 181 5.4 THE CHEMISTRY OF DISULFIDE CROSSLINKS 207
Amino acid side chains have predictable protonat.on Cystjne djsu|fides form readj|y ynder ^^
states _, ... conditions 207
Amino acid side chains mediate protein-protein Glutathione is an intracellular thiol buffer 207
interactions Cystine disulfides in proteins are in equilibrium
5.2 SOLID-PHASE PEPTIDE SYNTHESIS 185 with glutathione disulfides 208
Peptides can be used as pharmaceuticals 185 Combinatorial crosslinking and protein misfolding
Excess reagents and optimized chemistry allow high- can complicate attempts to produce disulfide-
throughput peptide synthesis 187 containing proteins 209
|*V3U -.B* ¦¦¦ * ¦
Concentrations of glutathione depend on location 210 Enzymes proceed via mechanisms with the minimum
5.5 PROTEIN DOMAINS HAVE STRUCTURAL number of different types of transition states 251
___~....^.^, , , nr Tin Serine proteases cleave amides by using an alkoxide
AND FUNCTIONAL ROLES 210
nucleophile 252
Biological protein assemblies exhibit hierarchical .. LT !. -,2+- . .. . .,
-._.. . Tin Metalloproteases use Zn^+ions to activate the
structures 210
nucleophilic water and stabilize the tetrahedral
The tertiary and quaternary structures of proteins . t ^,. ^ _,...
•j , ,. . . . . . . intermediate 253
access a wide range of different archetypal protein .*.-*• * i »• •» - r i
, . . 3 ... Activation can control protease activity 254
,, , . . p.... -,- Reversible enzyme inhibitors include transition-state
Zinc-finger domains recognize DNA sequences 212 . . ,7 . . . ~- -^ -,,-,-
Anumberofcommondomainsarebasedon analogs with very high affinity 255
B-sandwich architectures 213 Mechanism-based enzyme inhibitors react with
Calcium promotes interactions between cadherin residues at the active site 258
domains 215 Cooperative binding requires careful placement of
WD domains fit together like triangular slices of a cake 216
functional groups 260
. .. .. _,,, Triosephosphate isomerase is nearly a perfect
Collagen is formed from a three-stranded helix 216 enzvme 262
Protein kinase domains and seven-transmembrane
domains have key roles in signal transduction 217 6.4 ENZYMESTHAT USE ORGANIC COFACTORS 263
The RNA recognition motif domain binds to single- Enzyme cofactors extend the capabilities of enzymes 263
stranded RNA 218 Thiamine pyrophosphate provides a stabilized ylide 264
Peptide-binding domains can confer modular The dihydropyridine group of niacin (vitamin B3)
functions to proteins 218 provides a reactive hydride 265
5.6 HIGHER LEVELS OF PROTEIN STRUCTURE 219 The Pyridoxal C°faCt°r SerVeS aS a eleCtr°n Sink ^
The tertiary structure consists of one or more domains 219 6.5 ENGINEERING IMPROVED PROTEIN FUNCTION 269
Quaternary structure consists of highly integrated Protein engineering provides power tools for the
assemblies of independent, folded proteins 220 dissection of protein function and the development of
5.7 SUMMARY 221 hyperfunctional molecules 269
Alanine scanning assigns function to side chains
PROBLEMS 223 and motifs 269
Alanine scanning allows reverse engineering of
Chapter 6 ^ protein function 270
Protein Function 229 Protein engineering enables improvement of
6.1 RECEPTOR-LIGAND INTERACTIONS 229 Protein f nction 272
The thermodynamics and kinetics of receptor-ligand Protem engmeermg enables a change of protein
interactions govern all processes in biology 229 U?C l0? ,. . . ..... . .. .
Dose-response curves measure protein function, and Most random mutations debilitate rather than
correlate with affinity 232 enhance protein function 274
Highly specific protein-small-molecule interactions Recombination generates new combinations of
are useful 234 existing mutations 274
Screens work well for modest numbers of protein
6.2 A QUANTITATIVE VIEW OF ENZYME FUNCTION 236 variants, but exceptionally diverse libraries require
Enzymes are catalytic receptors 236 selections 275
Measurements of enzyme efficiency must account ,, n,lllllim,
for substrate binding and catalysis 238 6 SUMMARY 275
6.3 A MECHANISTIC VIEW OF ENZYMES THAT
CATALYZE MULTISTEP REACTIONS 240 Chapter 7
Protein kinases and proteases catalyze reactions Glycobiology 281
through multistep mechanisms 240
Protein kinases share a common motif 241 7 1 STRUCTURE 281
Regulation of protein kinase activity requires Tnere are 1 ° common monosaccharide building
allosteric binding 244 blocks for human glycans 281
Phosphorylation can also activate kinases 246 Grycobi°logy uses a compact form of nomenclature 283
Proteases serve roles in degradation and protein Po,ar effects and stereoelectronic effects determine
signaling 247 the relative stability of a and Panomers 284
Cysteine proteases catalyze amide hydrolysis by 7.2 THE CHEMISTRY AND ENZYMOLOGY OF THE
using a nucleophilic cysteine thiolate 250 GLYCOSIDE BOND 286
DETAILED CONTENTS xv
Monosaccharide carbonyl groups form hemiacetals 286 7.6 GLYCOSYLATIONINTHECYTOSOL 316
Six- and five-membered ring hemiacetals are O-glycosylation of proteins in the cytosol with
common 286 f GlcNAc is analogous to phosphorylation 316
Chemical hydrolysis of glycosidic bonds involves Drugs are targeted for export by glucuronidation 318
SN1 reactions 289 77 CHEMICAL SYNTHESIS OF OLIGOSACCHARIDES 318
Enzymatic hydrolysis of glycosidic bonds involves Anomeric stereochemistry is controlled by the
SN1-likeSN2 reactions 290 anomeric leaving group and the 2 substituent 318
Members of all classes of glycosylhydrolases have Modern oligosaccharide synthesis takes advantage
two carboxylic acids in the active site 290 0f activatable leaving groups 320
Substrate distortion is important in glycosylhydrolase Synthesis of oligosaccharides still requires a skilled
enzymes 291 synthetic organic chemist 321
Inhibiting glycosylhydrolase enzymes from viruses J£ pR0TE|NSTHAT B|NDT0 CARBOHYDRATE
can treat influenza 293 ilGANDS 322
Glycosyltransferases transfer monosaccharides from G|ycgns differentiate the surfaces of human ceNs 322
glycosyl phosphate donors 294
Most carbohydrate-binding proteins are multivalent 322
Glycosyltransferases transfer glycosyl groups from Human |ectjns mediate se|ectjve adhesion of
phosphates 294 |eukocytes 326
7.3 POLYSACCHARIDES 296 Human blood group antigens are found on
Diastereomers of glucose polymers have very glycolipids and glycoproteins 326
different properties 296 Some toxins enter cells through multivalent
Chitin is a resilient polymer in insect cuticles 297 carbohydrate recognition 327
Some tissues are cushioned by the polysaccharide Microarray technology facilitates the analysis of
hyaluronan 298 protein-glycan interactions 328
Meningococci are coated with polysialic acids like 79 GLUCOSE HOMEOSTASIS AND DIABETES 330
those found on neurons 298
Human metabolism and paper-burning are
7.4 GLYCOPROTEINS 299 related transformations 330
Glycosylate of human proteins occurs in the Glucose reacts with proteins over time 331
vesicles of the secretory pathway 299 Glucose-derived protein crosslinks are not
Synthesis of O-linked glycoproteins begins with the necessarily permanent 332
addition of xylose or N-acetylgalactose 300 There is a big market for artificial ligands for human
O-linked proteoglycans are polyanions 301 taste receptors 333
The carbohydrate moiety of N-linked glycoproteins 710 SUMMARY 335
is initially added as an oligosaccharide 303
PROBLEMS 337
Chapter 8
Polyketides and Terpenes 339
An Asn-Xxx-Ser motif adopts a reactive conformation
in the N-glycosylation of proteins 304
The processing of glycans occurs during vesicular
trafficking 305
A few human proteins are C-mannosylated on 81 THE CLAISEN REACTION IN POLYKETIDE
tryptophan residues 308 BIOSYNTHESIS 340
Glycosylate of proteins sometimes, but not always, jhe diverse structures of polyketide natural products
affects the intrinsic function of the protein 308 belie their iterative construction 340
Most extracellular signaling proteins are glycosylated Polyketides are derived from two-carbon and
with oligosaccharides 310 three-carbon building blocks 340
Many protein pharmaceuticals are glycosylated 310
Cell-cell recognition is often mediated by
glycoproteins 311
8.2 THE BIOSYNTHESIS OF FATTY ACIDS IS A
PARADIGM FOR POLYKETIDE BIOSYNTHESIS 342
, . ,.. . . ... .. .___, , , Fatty acids have varying levels of unsaturation 342
ntroduct on of N-g ycosylation sites can improve ¦ ... . . ...., 3 ... , . ,
. . - ,,•, Fatty acid/po yketide synthases are categorized
protein pharmaceuticals 312
on the basis of their supramolecular structure 343
Modified sugars can carry reactive groups through ^ ^.^ n ^^ ^
the glycoprotein biosynthesis pathway 312 ketjde chajn ^ ^ ^^ ^^ vvj^ ^
7.5 GLYCOLIPIDS 314 A transacylase loads monomeric subunits onto
Glycosphingolipids are lipid-like glycoconjugates 314 the carrier protein 344
Glycosylphosphatidylinositols from pathogens are Ketosynthases catalyze a decarboxylase Claisen
potential vaccines 315 condensation 345
Ketoreductases catalyze hydride transfer from Tail-to-tail coupling of terpenyl diphosphates
NADPH
345 generates precursors of higher-order terpenes 380
Dehydratases catalyze p-elimination 346 Polyene cyclizations generate many rings in a single
Enoyl reductases catalyze a conjugate reduction 346 reaction 381
A thioesterase uses a catalytic triad to cleave the Humans lack genes for retinoid biosynthesis 383
acyl group from the acyl carrier protein 347 g? N0NHUMANTERPENE NATURAL PRODUCTS 385
Enzymes associated with the endoplasmic reticulum p|gnts gnd microorganisms produce a much wider
put the finishing touches on fatty acids 348 rangeofterpene natural products than humans 385
8.3 THE BIOLOGICAL ROLE OF HUMAN Isomerization of geranyl diphosphate to linalyl
POLYKETIDES 348 diphosphate facilitates cyclization 386
Eight categories of lipids are found in biology 348 The 2-norbornyl cation exhibits exceptional behavior 388
Lipid membranes are composed of lipids with a Minor products offer clues to the enzymatic
polar head group and a nonpolar tail 348 mechanisms of terpene cyclases 389
The lipid bilayer entropically favors interactions between Some terpene cyclases generate medium-sized rings 390
embedded molecules 350 The biosynthesis of some terpenes involves
Phospholipases generate distinct chemical signals nontraditional [1,3] hydride shifts 391
by hydrolyzing various bonds of phospholipids 350 p|ants can a|so ma| e complex triterpenes from
Phospholipase CB generates two signaling molecules 351 squalene 391
Arachidonic acids are converted into diverse signaling Hyperthermophilic archaebacteria produce cyclic
molecules during inflammation 352 lipids from terpenes 392
Sphingosine derivatives are important in intracellular
signaling 355 8.8 SUMMARY 393
Metal-catalyzed hydrogenation of unsaturated fats PROBLEMS 394
changed the human diet 357
Some lipids from lower organisms contain Chanter 9
cyclopropane rings 358 _. . . _ ^ , . _. . _ . .. _«.,
Acylation of human proteins induces membrane Chemical Control of Signal Transduction 397
localization 359
9.1 SIGNALTRANSDUCTION 399
Chemical transformation of fats generates useful ,. . . , . ... , 3QQ
, 3 Chemical signaling is universal 399
The field of biology is full of cryptic acronyms and
8.4 NONHUMAN POLYKETIDE NATURAL ambiguous symbols 399
PRODUCTS 362 Fast cellular responses do not involve the
Several tricks amplify the potential diversity of production of proteins 401
polyketide natural products 362 Cell contraction and vesicle fusion: fast calcium-
Streptomyces has mastered polyketide biosynthesis 364 dependent responses that do not involve changes
The modular genetic organization of type I in transcription 402
polyketide synthases facilitates genetic Cell signaling can involve pathways within cells
reprogramming 366 and/or between cells 403
Sometimes additional methyl groups are added to 92 AN OVERVIEW OF SIGNAL TRANSDUCTION
the polyket.de backbone 369 PATHWAYS IN HUMAN CELLS 404
8.5 NONRIBOSOMAL PEPTIDE SYNTHASES 369 There are seven major signal transduction pathways
Ribosomal translation is suited to the production in humans 404
of large proteins, not short peptides 369 Chemical genetics involves the use of small
Most bioactive peptide secondary metabolites are molecules to understand gene function 405
generated by peptide synthases, not by ribosomes 370 Screening identifies small molecules for use in
8.6 HUMAN TERPENES 371 chemical genetics 406
Eariy chemists recognized terpenes as oligomers of 9.3 NUCLEAR RECEPTORS 407
isoprene 371 Binding of small-molecule ligands activates nuclear
Cationic additions lead to linear chains 372 receptor transcription factors 407
Prenyl subunits arise through enolate chemistry 373 Some nuclear receptors translocate from cytoplasm
Inhibition of terpene biosynthesis is the number one to the nucleus, and bind DNA as homodimers 409
treatment for heart disease 375 Some nuclear receptors are localized in the nucleus
cheS qum°nes serve lmDortant ro|esl edox and bind to DNA as heterodimers 409
d^iT*:^^ r 377 The mode of nuclear receptor dimerization
Prenylat,on of protems confers membrane affinity 379 determines DNA sequence selectivity 410
DETAILED CONTENTS xvii
Human cells can be rewired for control by Drosophila High-affinity ligand-receptor interactions lead to
nuclear receptors 411 slow response times and low dynamic range 432
Steroids make highly potent pharmaceuticals 412 G proteins allow low-affinity receptors to have high
Nonsteroidal ligands for nuclear receptors are sensitivity 433
also widely used as drugs 413 Seven-transmembrane domain G protein-coupled
Drugs can be designed to target specific mutations receptors can respond to a wide range of ligands
of nuclear receptors 414 with high dynamic range 434
9.4 CELL-SURFACE RECEPTORS THAT INTERACT Heterotrimeric G proteins are designed to generate
DIRECTLY WITH TRANSCRIPTION FACTORS 415
divergent signals 434
Hematopoietic proliferation and differentiation are Some elements of si9nal transduction pathways can
controlled by molecular signals 415
Human cytokines can be used as pharmaceuticals 416
The JAK-STAT pathway involves a receptor, a kinase,
integrate inputs 434
Contraction of endothelial smooth muscle is
controlled by Gctq 436
and a transcription factor 417 Some bacterial toxins reprogram Ga subunits, with
Small-molecule dimerizers can be used to demonstrate
deadly results 437
functional relationships between proteins 418 Adenylyl cyclase.and p^°i?° ip?*e CP are the mOSt ao
Other interferons bind to heterodimeric and higher- T ^ ^ °f ?™ ™,™ n u
order receptor assemblies 419 Many Pharmaceuticals act on 7TM GPCRs that
Synthetic A/-hydroxysuccinimidyl esters can acylate n resp°nd to l,gi!?ds^ veJ fr°m *m,no a°ds .A 43*
proteins in aqueous solution 419 Opioids act on 7TM GPCRs that bind to neuropeptides 440
T ^ , *U t * a * Smell and taste involve 7TM GPCRs 441
Transforming growth factor-p receptors possess ,, , ...
u -i* • ¦ /.l i. 7 . .-, How do you bind to a photon? 442
built-in serine/threonine kinase domains 421 ,.._,... . ,. , , .
The decision between immortality and destiny
9.5 RECEPTOR TYROSINE KINASES 421 involves the protein Wnt and the B-catenin pathway 443
Receptor tyrosine kinases control tissue growth 421 A seven-transmembrane receptor that controls
Growth factors have a role in proliferation of development does not bind to an extracellular
urothelial cells 422 ligand 444
Comparing receptor tyrosine kinases and cytokine ION CHANNEL RECEPTORS 445
receptors reveals useful commonalities 423 ...
tl a-™ u- j- -4. r * * • i • Ion channel receptors provide an u tra-fast response
The ATP-bmding sites of receptor tyrosine kinases are r aas
sufficiently different that they can be selectively . ,°s Imu . , , ...
• uu* ju. n ii *- * A human cell is a bag of potassium in a saty ocean 446
inhibited by small molecules 424 ... ,. r , ..
_ . . , ... ,. ., Votage-gated ion channes are activated by
Transphosphorylation of tyrosine residues is . ..«¦ .
. . 424 transmembrane differences in ion concentrations 447
R^r tyrosine kinases signal growth via a MAP Pentameric Cys-loop receptors are gated by
neurotransmitters 449
The nicotinic acetylcholine receptor is a popular
target for toxins 450
kinase cascade 425
Many signal transduction pathways involve abundant
small molecules and scarce proteins 426 ._ ., . . .£....
Receptor tyrosine kinases turn on calcium signaling Tetrameric g utamate receptors are defined by their
pathways via phospholipase C 428 sPec,ficity for 9lutamate analo9s 451
Receptor tyrosine kinases broadcast both proliferative 9.8 TRIMERIC DEATH RECEPTORS 451
and anti-apoptotic signals via Akt 429 Tumor necrosis factor binding toTNF receptors
The differences between various receptor tyrosine triggers diverse, cell-dependent responses 451
kinase pathways are less important than the g Q pATHWAYS CONTROLLED BY SMALL
simi arities . 430 DIFFUSIBLE GAS MOLECULES 453
Chemical methods for isolation and identification _ , .....,,.
of kinase substrates 430 0xy9en levJels are monitored through HIF-la 453
A nitric oxide receptor induces the production
9.6 G PROTEIN-COUPLED RECEPTORS 431 ofcGMP 454
9.10 SUMMARY 455
Seven-transmembrane domain G protein-coupled
receptors can respond to a wide range of ligands
with high dynamic range 431 PROBLEMS 456
|
| any_adam_object | 1 |
| author | Van Vranken, David L. Weiss, Gregory A. |
| author_GND | (DE-588)1030300488 (DE-588)1030301530 |
| author_facet | Van Vranken, David L. Weiss, Gregory A. |
| author_role | aut aut |
| author_sort | Van Vranken, David L. |
| author_variant | v d l v vdl vdlv g a w ga gaw |
| building | Verbundindex |
| bvnumber | BV040908358 |
| classification_rvk | VK 8500 WD 5000 |
| classification_tum | CHE 800f |
| ctrlnum | (OCoLC)844040388 (DE-599)OBVAC10721116 |
| dewey-full | 572 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 572 - Biochemistry |
| dewey-raw | 572 |
| dewey-search | 572 |
| dewey-sort | 3572 |
| dewey-tens | 570 - Biology |
| discipline | Chemie / Pharmazie Biologie Chemie |
| format | Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01885nam a2200457zc 4500</leader><controlfield tag="001">BV040908358</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20211124 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">130325s2013 a||| |||| 00||| eng d</controlfield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">9780815342144</subfield><subfield code="c">(pbk.) £48.00</subfield><subfield code="9">978-0-8153-4214-4</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">0815342144</subfield><subfield code="c">(pbk.) £48.00</subfield><subfield code="9">0-8153-4214-4</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)844040388</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)OBVAC10721116</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-91G</subfield><subfield code="a">DE-355</subfield><subfield code="a">DE-19</subfield><subfield code="a">DE-20</subfield><subfield code="a">DE-83</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">572</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">VK 8500</subfield><subfield code="0">(DE-625)147535:253</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">WD 5000</subfield><subfield code="0">(DE-625)148184:</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">CHE 800f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Van Vranken, David L.</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1030300488</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Introduction to bioorganic chemistry and chemical biology</subfield><subfield code="c">David Van Vranken and Gregory Weiss</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">New York ; London</subfield><subfield code="b">Garland Science, Taylor & Francis Group</subfield><subfield code="c">[2013]</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Boca Raton ; London ; New York</subfield><subfield code="b">CRC Press, Taylor & Francis Group</subfield></datafield><datafield tag="264" ind1=" " ind2="4"><subfield code="c">© 2013</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XVII, 486 S.</subfield><subfield code="b">Ill.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Chemische Biologie</subfield><subfield code="0">(DE-588)7657972-4</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Naturstoffchemie</subfield><subfield code="0">(DE-588)4171332-1</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Biochemie</subfield><subfield code="0">(DE-588)4006777-4</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="653" ind1=" " ind2=" "><subfield code="a">Biochemistry.</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Biochemie</subfield><subfield code="0">(DE-588)4006777-4</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="1"><subfield code="a">Naturstoffchemie</subfield><subfield code="0">(DE-588)4171332-1</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="2"><subfield code="a">Chemische Biologie</subfield><subfield code="0">(DE-588)7657972-4</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="C">b</subfield><subfield code="5">DE-604</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Weiss, Gregory A.</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1030301530</subfield><subfield code="4">aut</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025887737&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-025887737</subfield></datafield></record></collection> |
| id | DE-604.BV040908358 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T00:35:02Z |
| institution | BVB |
| isbn | 9780815342144 0815342144 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-025887737 |
| oclc_num | 844040388 |
| open_access_boolean | |
| owner | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-20 DE-83 |
| owner_facet | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-20 DE-83 |
| physical | XVII, 486 S. Ill. |
| publishDate | 2013 |
| publishDateSearch | 2013 |
| publishDateSort | 2013 |
| publisher | Garland Science, Taylor & Francis Group CRC Press, Taylor & Francis Group |
| record_format | marc |
| spelling | Van Vranken, David L. Verfasser (DE-588)1030300488 aut Introduction to bioorganic chemistry and chemical biology David Van Vranken and Gregory Weiss New York ; London Garland Science, Taylor & Francis Group [2013] Boca Raton ; London ; New York CRC Press, Taylor & Francis Group © 2013 XVII, 486 S. Ill. txt rdacontent n rdamedia nc rdacarrier Chemische Biologie (DE-588)7657972-4 gnd rswk-swf Naturstoffchemie (DE-588)4171332-1 gnd rswk-swf Biochemie (DE-588)4006777-4 gnd rswk-swf Biochemistry. Biochemie (DE-588)4006777-4 s Naturstoffchemie (DE-588)4171332-1 s Chemische Biologie (DE-588)7657972-4 s b DE-604 Weiss, Gregory A. Verfasser (DE-588)1030301530 aut HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025887737&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Van Vranken, David L. Weiss, Gregory A. Introduction to bioorganic chemistry and chemical biology Chemische Biologie (DE-588)7657972-4 gnd Naturstoffchemie (DE-588)4171332-1 gnd Biochemie (DE-588)4006777-4 gnd |
| subject_GND | (DE-588)7657972-4 (DE-588)4171332-1 (DE-588)4006777-4 |
| title | Introduction to bioorganic chemistry and chemical biology |
| title_auth | Introduction to bioorganic chemistry and chemical biology |
| title_exact_search | Introduction to bioorganic chemistry and chemical biology |
| title_full | Introduction to bioorganic chemistry and chemical biology David Van Vranken and Gregory Weiss |
| title_fullStr | Introduction to bioorganic chemistry and chemical biology David Van Vranken and Gregory Weiss |
| title_full_unstemmed | Introduction to bioorganic chemistry and chemical biology David Van Vranken and Gregory Weiss |
| title_short | Introduction to bioorganic chemistry and chemical biology |
| title_sort | introduction to bioorganic chemistry and chemical biology |
| topic | Chemische Biologie (DE-588)7657972-4 gnd Naturstoffchemie (DE-588)4171332-1 gnd Biochemie (DE-588)4006777-4 gnd |
| topic_facet | Chemische Biologie Naturstoffchemie Biochemie |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025887737&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT vanvrankendavidl introductiontobioorganicchemistryandchemicalbiology AT weissgregorya introductiontobioorganicchemistryandchemicalbiology |