Carbohydrate-based drug discovery:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Weinheim
Wiley-VCH
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| ISBN: | 3527306323 |
Internformat
MARC
| LEADER | 00000nam a2200000 ca4500 | ||
|---|---|---|---|
| 001 | BV017502707 | ||
| 003 | DE-604 | ||
| 005 | 20050707 | ||
| 007 | t | ||
| 008 | 030917nuuuuuuuugw |||| 00||| eng d | ||
| 016 | 7 | |a 966548892 |2 DE-101 | |
| 020 | |a 3527306323 |9 3-527-30632-3 | ||
| 035 | |a (DE-599)BVBBV017502707 | ||
| 040 | |a DE-604 |b ger |e rakddb | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c DE | ||
| 084 | |a VS 5350 |0 (DE-625)147687:253 |2 rvk | ||
| 084 | |a MED 920f |2 stub | ||
| 084 | |a CIT 840f |2 stub | ||
| 084 | |a CHE 893f |2 stub | ||
| 084 | |a CHE 850f |2 stub | ||
| 245 | 1 | 0 | |a Carbohydrate-based drug discovery |c Chi-Huey Wong (Ed.) |
| 264 | 1 | |a Weinheim |b Wiley-VCH | |
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 0 | 7 | |a Kohlenhydrate |0 (DE-588)4164517-0 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Chemie |0 (DE-588)4009816-3 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Arzneimittelforschung |0 (DE-588)4003120-2 |2 gnd |9 rswk-swf |
| 689 | 0 | 0 | |a Arzneimittelforschung |0 (DE-588)4003120-2 |D s |
| 689 | 0 | 1 | |a Kohlenhydrate |0 (DE-588)4164517-0 |D s |
| 689 | 0 | 2 | |a Chemie |0 (DE-588)4009816-3 |D s |
| 689 | 0 | |5 DE-604 | |
| 700 | 1 | |a Wong, Chi-Huey |e Sonstige |4 oth | |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=012750688&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 943 | 1 | |a oai:aleph.bib-bvb.de:BVB01-012750688 | |
Datensatz im Suchindex
| _version_ | 1808044924829958144 |
|---|---|
| adam_text |
V
CONTENTS
VOLUME
1
PREFACE
XXV
LIST
OF
CONTRIBUTORS
XXVII
1
SYNTHETIC
METHODOLOGIES
1
CHIKAKO
SAOTOME
AND
OSAMU
KANIE
1.1
INTRODUCTION
1
1.2
TACTICAL
ANALYSIS
FOR
OVERALL
SYNTHETIC
EFFICIENCY
1
1.3
METHODOLOGICAL
IMPROVEMENTS
2
1.3.1
CHEMISTRY
3
1.3.2
PROTECTING
GROUP
MANIPULATIONS
4
1.3.3
MODULATION
OF
THE
REACTIVITY
OF
GLYCOSYL
DONORS
6
1.3.4
BLOCK
SYNTHESIS
8
1.4
ACCESSIBILITY
11
1.4.1
SOLUTION-BASED
CHEMISTRY
11
1.4.2
ONE-POT
GLYCOSYLATION
13
1.4.3
SOLID-PHASE
CHEMISTRY
16
1.4.3.1
FUNDAMENTALS
OF
SOLID-PHASE
OLIGOSACCHARIDE
SYNTHESIS
16
1.4.3.2
THE
SUPPORT
16
1.4.3.3
LINKERS
TO
THE
SUPPORT
20
1.4.3.4
PROTECTING
GROUPS
USED
IN
SOLID-PHASE
OLIGOSACCHARIDE
SYNTHESIS
20
1.4.3.5
SOLID-PHASE
OLIGOSACCHARIDE
SYNTHESIS
20
1.4.3.6
MONITORING
OF
REACTION
PROGRESS
26
1.4.4
AUTOMATION
29
1.5
CONCLUDING
REMARKS
32
1.6
REFERENCES
33
2
COMPLEX
CARBOHYDRATE
SYNTHESIS
37
MAKOTO
KISO,
HIDEHARU
ISHIDA,
AND
HIROMUNE
ANDO
2.1
INTRODUCTION
37
2.2
SYNTHETIC
GANGLIOSIDES
38
2.2.1
GANGLIOSIDES
GM4
AND
GM3,
AND
THEIR
ANALOGUES
AND
DERIVATIVES
38
VI
I
CONTENTS
2.2.2
2.2.3
2.2.3.1
2.2.3.2
2.2.4
2.2.4.1
2.2.4.2
2.3
2.4
2.5
SIALYLPARAGLOBOSIDE
(SPG)
ANALOGUES
AND
DERIVATIVES
40
SELECTIN
LIGANDS
43
SIALYL
LEWIS
X
44
NOVEL
6-SUIFO
SLE
X
VARIANTS
45
SIGLEC
LIGANDS
46
CHOL-1
(A-SERIES)
GANGLIOSIDES
47
NOVEL
SULFATED
GANGLIOSIDES
50
TOXIN
RECEPTOR
50
SUMMARY
AND
PERSPECTIVES
52
REFERENCES
52
3
THE
CHEMISTRY
OF
SIALIC
ACID
55
GEERT-JAN
BOONS
AND
ALEXEI
V
DEMCHENKO
3.1
3.2
3.3
3.3.1
3.3.1.1
3.3.1.2
3.3.1.3
3.3.1.3
3.3.1.4
3.3.2
INTRODUCTION
55
CHEMICAL
AND
ENZYMATIC
SYNTHESIS
OF
SIALIC
ACIDS
56
CHEMICAL
GLYCOSIDATION
OF
SIALIC
ACIDS
59
DIRECT
CHEMICAL
SIALYLATIONS
60
2-CHLORO
DERIVATIVES
AS
GLYCOSYL
DONORS
61
2-THIO
DERIVATIVES
AS
GLYCOSYL
DONORS
62
2-XANTHATES
AS
GLYCOSYL
DONORS
69
2-PHOSPHITES
AS
GLYCOSYL
DONORS
71
MISCELLANEOUS
DIRECT
CHEMICAL
METHODS
71
INDIRECT
CHEMICAL
METHODS
WITH
THE
USE
OF
A
PARTICIPATING
AUXILIARY
AT
C-3
73
3.3.2.1
3.3.2.2
3.3.3
3.4
3.4.1
3.4.1.1
3.4.2
3.5
3.6
3.7
3-BROMO
AND
OTHER
3-0
AUXILIARIES
73
3-THIO
AND
3-SELENO
AUXILIARIES
74
SYNTHESIS
OF
(2- 8)-LINKED
SIALOSIDES
77
ENZYMATIC
GLYCOSIDATIONS
OF
SIALIC
ACIDS
83
SIALYLTRANSFERASES
84
METABOLIC
ENGINEERING
OF
THE
SIALIC
ACID
BIOSYNTHETIC
PATHWAY
90
SIALIDASES
90
SYNTHESIS
OF
C
AND
S-GLYCOSIDES
OF
SIALIC
ACID
91
MODIFICATIONS
AT
N-5
94
REFERENCES
95
4
SOLID-PHASE
OLIGOSACCHARIDE
SYNTHESIS
103
PETER
H.
SEEBERGER
4.1
4.2
4.3
4.3.1
4.3.2
4.3.3
4.4
4.4.1
INTRODUCTION
103
PIONEERING
EFFORTS
IN
SOLID-PHASE
OLIGOSACCHARIDE
SYNTHESIS
104
SYNTHETIC
STRATEGIES
105
IMMOBILIZATION
OF
THE
GLYCOSYL
ACCEPTOR
106
IMMOBILIZATION
OF
THE
GLYCOSYL
DONOR
106
BI-DIRECTIONAL
STRATEGY
107
SUPPORT
MATERIALS
107
INSOLUBLE
SUPPORTS
107
CONTENTS
VII
4.4.2
SOLUBLE
SUPPORTS
108
4.5
LINKERS
108
4.5.1
SILYL
ETHERS
108
4.5.2
ACID
AND
BASE-LABILE
LINKERS
109
4.5.3
THIOGLYCOSIDE
LINKERS
110
4.5.4
LINKERS
CLEAVED
BY
OXIDATION
110
4.5.5
PHOTOCLEAVABLE
LINKERS
111
4.5.6
LINKERS
CLEAVED
BY
OLEFIN
METATHESIS
111
4.6
SYNTHESIS
OF
OLIGOSACCHARIDES
ON
SOLID
SUPPORT
BY
USE
OF
DIFFERENT
GLYCOSYLATING
AGENTS
112
4.6.1
1,2-ANHYDROSUGARS
-
THE
GLYCAL
ASSEMBLY
APPROACH
112
4.6.2
GLYCOSYL
SULFOXIDES
113
4.6.3
GLYCOSYL
TRICHLOROACETIMIDATES
114
4.6.4
THIOGLYCOSIDES
115
4.6.5
GLYCOSYL
FLUORIDES
118
4.6.6
N-PENTENYL
GLYCOSIDES
118
4.6.7
GLYCOSYL
PHOSPHATES
118
4.7
AUTOMATED
SOLID-PHASE
OLIGOSACCHARIDE
SYNTHESIS
118
4.7.1
FUNDAMENTAL
CONSIDERATIONS
119
4.7.2
AUTOMATED
SYNTHESIS
WITH
GLYCOSYL
TRICHLOROACETIMIDATES
121
4.7.3
AUTOMATED
SYNTHESIS
WITH
GLYCOSYL
PHOSPHATES
121
4.7.4
AUTOMATED
OLIGOSACCHARIDE
SYNTHESIS
BY
USE
OF
DIFFERENT
GLYCOSYLATING
AGENTS
121
4.7.5
"
CAP-TAGS
"
TO
SUPPRESS
DELETION
SEQUENCES
123
4.7.6
CURRENT
STATE
OF
THE
ART
OF
AUTOMATED
SYNTHESIS
123
4.8
CONCLUSION
AND
OUTLOOK
124
4.9
REFERENCES
125
5
SOLUTION
AND
POLYMER-SUPPORTED
SYNTHESIS
OF
CARBOHYDRATES
129
SHIN-ICHIRO
NISHIMURA
5.1
INTRODUCTION
129
5.2
MIMICKING
GLYCOPROTEIN
BIOSYNTHETIC
SYSTEMS
130
5.3
REFERENCES
136
6
ENZYMATIC
SYNTHESIS
OF
OLIGOSACCHARIDES
JIANBO
ZHANG,
JUN
SHAO,
PREZEMK
KOWAL,
AND
PENG
GEORGE
WANG
6.1
INTRODUCTION
137
6.2
SUGAR
NUCLEOTIDE
BIOSYNTHETIC
PATHWAYS
140
6.2.1
BASIC
PRINCIPLE
140
6.2.2
REGENERATION
SYSTEMS
FOR
NINE
COMMON
SUGAR
NUCLEOTIDES
142
6.2.2.1
REGENERATION
SYSTEMS
FOR
UDP-GAL,
UDP-GLC,
UDP-GLCA
AND
UDP-XYL
142
6.2.2.2
REGENERATION
SYSTEMS
FOR
UDP-GLCNAC
AND
UDP-GALNAC
144
6.2.2.3
REGENERATION
SYSTEMS
FOR
GDP-MAN
AND
GDP-FUC
147
6.2.2.4
CMP-NEU5AC
REGENERATION
149
VIII
I
CONTENTS
6.2.3
6.3
6.3.1
6.3.1.1
6.3.1.2
6.3.2
6.3.2.1
6.3.2.2
6.3.2.3
6.4
6.5
NOVEL
ENERGY
SOURCE
IN
SUGAR
NUCLEOTIDE
REGENERATION
150
ENZYMATIC
OLIGOSACCHARIDE
SYNTHESIS
PROCESSES
151
CELL-FREE
OLIGOSACCHARIDE
SYNTHESIS
151
IMMOBILIZED
GLYCOSYLTRANSFERASES
AND
WATER-SOLUBLE
GLYCOPOLYMER
152
"
SUPERBEADS
"
154
LARGE-SCALE
SYNTHESES
OF
OLIGOSACCHARIDES
WITH
WHOLE
CELLS
156
KYOWA
HAKKO
'
S
TECHNOLOGY
157
WANG
'
S
"
SUPERBUG
"
157
OTHER
WHOLE
CELL-BASED
TECHNOLOGIES
161
FUTURE
DIRECTIONS
162
REFERENCES
162
7
GLYCOPEPTIDES
AND
GLYCOPROTEINS:
SYNTHETIC
CHEMISTRY
AND
BIOLOGY
169
OLIVER
SEITZ
7.1
7.2
7.3
7.4
7.4.1
7.4.2
7.4.2.1
7.4.2.2
7.5
7.5.1
7.5.2
7.5.3
7.5.4
7.6
7.6.1
7.6.2
7.6.3
7.6.4
7.7
7.8
INTRODUCTION
169
THE
GLYCOSIDIC
LINKAGE
169
THE
CHALLENGES
OF
GLYCOPEPTIDE
SYNTHESIS
171
SYNTHESIS
OF
PREFORMED
GLYCOSYL
AMINO
ACIDS
173
N-GLYCOSIDES
173
O-GLYCOSIDES
176
O-GLYCOSYL
AMINO
ACIDS
BEARING
MONO
OR
DISACCHARIDES
176
O-GLYCOSYL
AMINO
ACIDS
BEARING
COMPLEX
CARBOHYDRATES
179
SYNTHESIS
OF
GLYCOPEPTIDES
181
N-GLYCOPEPTIDE
SYNTHESIS
IN
SOLUTION
181
O-GLYCOPEPTIDE
SYNTHESIS
IN
SOLUTION
185
SOLID-PHASE
SYNTHESIS
OF
N-GLYCOPEPTIDES
188
SOLID-PHASE
SYNTHESIS
OF
O-GLYCOPEPTIDES
192
BIOLOGICAL
AND
BIOPHYSICAL
STUDIES
200
CONFORMATIONS
OF
GLYCOPEPTIDES
200
GLYCOPEPTIDES
AS
SUBSTRATES
OF
ENZYMES
AND
RECEPTORS
203
GLYCOPEPTIDES
AND
CANCER
IMMUNOTHERAPY
204
GLYCOPEPTIDES
AND
T
CELL
RECOGNITION
206
SUMMARY
AND
OUTLOOK
208
REFERENCES
209
8
SYNTHESIS
OF
COMPLEX
CARBOHYDRATES:
EVERNINOMICIN
13,384-1
215
K.
C.
NICOLAOU,
HELEN
J.
MITCHELL,
AND
SCOTT
A.
SNYDER
8.1
8.2
8.2.1
8.2.2
8.3
8.3.1
8.3.1.1
8.3.1.2
INTRODUCTION
215
RETROSYNTHETIC
ANALYSIS
AND
STRATEGY
218
OVERVIEW
OF
SYNTHETIC
STRATEGIES
AND
METHODOLOGIES
218
RETROSYNTHETIC
ANALYSIS:
OVERALL
APPROACH
222
TOTAL
SYNTHESIS
OF
EVERNINOMICIN
13,384-1
(1)
223
APPROACHES
TOWARDS
THE
A!B(A)C
FRAGMENT
223
INITIAL
MODEL
STUDIES
223
CONSTRUCTION
OF
THE
BUILDING
BLOCKS
225
CONTENTS
I
IX
8.3.1.3
ASSEMBLY
AND
COMPLETION
OF
THE
A^AJC
FRAGMENT
229
8.3.2
CONSTRUCTION
OF
THE
FGHA
2
FRAGMENT
231
8.3.2.1
FIRST
GENERATION
APPROACH
TO
THE
FGHA
2
FRAGMENT
231
8.3.2.2
SECOND
GENERATION
STRATEGY
TOWARDS
THE
FGHA
2
FRAGMENT
232
8.3.2.3
ASSEMBLY
OF
THE
FGHA
2
FRAGMENT
235
8.3.3
CONSTRUCTION
OF
THE
DE
DISACCHARIDE
241
8.3.3.1
RETROSYNTHETIC
ANALYSIS
AND
CONSTRUCTION
OF
BUILDING
BLOCKS
FOR
THE
DE
FRAGMENT
241
8.3.3.2
ASSEMBLY
OF
THE
DE
FRAGMENT
243
8.3.3.3
TEST
OF
STRATEGIES
244
8.3.4
ASSEMBLY
OF
THE
DEFGHA
2
FRAGMENT
245
8.3.5
COMPLETION
OF
THE
TOTAL
SYNTHESIS
OF
EVERNINOMICIN
13,384-1
247
8.4
CONCLUSION
249
8.5
REFERENCES
250
9
CHEMICAL
SYNTHESIS
OF
ASPARAGINE-LINKED
GLYCOPROTEIN
OLIGOSACCHARIDES:
RECENT
EXAMPLES
253
YUKISHIGE
ITO
AND
ICHIRO
MATSUO
9.1
INTRODUCTION
253
9.2
SYNTHESIS
OF
ASN-LINKED
OLIGOSACCHARIDES:
BASIC
PRINCIPLES
257
9.3
CHEMICAL
SYNTHESIS
OF
COMPLEX
OLIGOSACCHARIDES
261
9.3.1
CLASSICAL
EXAMPLES
261
9.3.2
TRICHLOROACETIMIDATE
APPROACH
TO
COMPLEX-TYPE
GLYCAN
CHAINS
265
9.3.3
N-PENTENYL
GLYCOSIDES
AS
GLYCOSYL
DONORS
265
9.3.4
GLYCAL
APPROACH
TO
COMPLEX
OLIGOSACCHARIDES
267
9.3.5
INTRAMOLECULAR
AGLYCON
DELIVERY
APPROACH
269
9.3.6
NEW
PROTECTING
GROUP
STRATEGY
273
9.3.7
LINEAR
SYNTHESIS
OF
BRANCHED
OLIGOSACCHARIDE
274
9.3.8
CHEMOENZYMATIC
APPROACH
TO
COMPLEX-TYPE
GLYCANS
275
9.4
REFERENCES
278
10
CHEMISTRY
AND
BIOCHEMISTRY
OF
ASPARAGINE-LINKED
PROTEIN
GLYCOSYLATION
281
BARBARA
IMPERIALI
AND
VINCENT
W.-F.
TAI
10.1
PROTEIN
GLYCOSYLATION
281
10.1.1
INTRODUCTION
281
10.1.2
ASPARAGINE-LINKED
GLYCOSYLATION
AND
OLIGOSACCHARYL
TRANSFERASE
281
10.2
SMALL-MOLECULE
PROBES
OF
THE
BIOCHEMISTRY
OF
OLIGOSACCHARYL
TRANSFERASE
283
10.2.1
PHOTOAFFINITY
AND
AFFINITY
LABELING
OF
OLIGOSACCHARYL
TRANSFERASE
284
10.2.2
INVESTIGATION
OF
PEPTIDE-BASED
SUBSTRATE
ANALOGUES
AS
INHIBITORS
OF
OLIGOSACCHARYL
TRANSFERASE
287
10.2.2.1
INHIBITORS
OF
N-LINKED
GLYCOSYLATION
AND
GLYCOPROTEIN
PROCESSING
287
10.2.2.2
PEPTIDE-BASED
ANALOGUES
AND
INHIBITORS
288
10.2.2.3
INTERIM
SUMMARY
292
X
CONTENTS
10.2.3
INVESTIGATION
OF
CARBOHYDRATE-BASED
SUBSTRATE
ANALOGUES
AS
PROBES
OF
OLIGOSACCHARYL
TRANSFERASE
FUNCTION
292
10.2.3.1
10.2.3.2
POSSIBLE
MECHANISMS
FOR
GLYCOSYL
TRANSFER
294
PROBING
OF
THE
MECHANISM
OF
OLIGOSACCHARYL
TRANSFERASE
WITH
POTENTIAL
INHIBITORS
296
10.2.3.3
10.3
10.4
INTERIM
SUMMARY
300
CONCLUSIONS
301
REFERENCES
301
11
CONFORMATIONAL
ANALYSIS
OF
C-CLYCOSIDES
AND
RELATED
COMPOUNDS:
PROGRAMMING
CONFORMATIONAL
PROFILES
OF
C
AND
O-CLYCOSIDES
305
PETER
G.
GOEKJIAN,
ALEXANDER
WEI,
AND
YOSHITO
KISHI
11.1
11.2
11.3
INTRODUCTION
305
STEREOELECTRONIC
EFFECTS
AND
THE
EXO-ANOMERIC
CONFORMATION
306
CONFORMATIONAL
ANALYSIS
OF
C-GLYCOSIDES:
C-MONOGLYCOSIDES
309
11.4
1,4-LINKED
C-DISACCHARIDES:
THE
IMPORTANCE
OF
SYN
PENTANE
INTERACTIONS
314
11.5
PREDICTION
OF
CONFORMATIONAL
PREFERENCE
AND
EXPERIMENTAL
VALIDATION
318
11.6
11.7
PROGRAMMING
OLIGOSACCHARIDE
CONFORMATION
322
CONFORMATIONAL
DESIGN
OF
C-TRISACCHARIDES
BASED
ON
A
HUMAN
BLOOD
GROUP
ANTIGEN
323
11.8
11.8.1
11.8.2
11.9
11.10
11.11
CONFORMATIONAL
DESIGN:
RELATIONSHIP
TO
BIOLOGICAL
ACTIVITY
330
C-LACTOSE
VS.
O-LACTOSE
331
HUMAN
BLOOD
GROUP
TRISACCHARIDES
334
CONCLUDING
REMARKS
336
ACKNOWLEDGEMENTS
337
REFERENCES
337
12
SYNTHETIC
LIPID
A
ANTAGONISTS
FOR
SEPSIS
TREATMENT
341
WILLIAM
J.
CHRIST,
LYNN
D.
HAWKINS,
MICHAEL
D.
LEWIS,
AND
YOSHITO
KISHI
12.1
12.2
12.2.1
12.2.2
12.2.3
12.3
12.4
12.5
BACKGROUND
341
HYPOTHESIS
AND
APPROACH
342
MONOSACCHARIDE
ANTAGONISTS:
LIPID
X
ANALOGUES
343
DISACCHARIDE
ANTAGONIST
OF
LIPID
A:
FIRST
GENERATION
344
DISACCHARIDE
ANTAGONIST
OF
LIPID
A:
SECOND
GENERATION
348
CONCLUSION
351
ACKNOWLEDGEMENT
353
REFERENCES
353
13
POLYSIALIC
ACID
VACCINES
357
HAROLD
J.
JENNINGS
13.1
13.2
INTRODUCTION
357
GROUP
C
MENINGOCOCCAL
VACCINES
358
CONTENTS
I
XI
13.2.1
STRUCTURE
AND
IMMUNOLOGY
OF
GCMP
358
13.2.2
GROUP
C
CONJUGATE
VACCINES
360
13.3
GROUP
B
MENINGOCOCCAL
VACCINES
362
13.3.1
STRUCTURE
OF
GBMP
362
13.3.2
IMMUNOLOGY
OF
GBMP
362
13.3.3
B
POLYSACCHARIDE-PROTEIN
CONJUGATES
363
13.3.4
EXTENDED
HELICAL
EPITOPE
OF
PSA
364
13.4
CHEMICALLY
MODIFIED
GROUP
B
MENINGOCOCCAL
VACCINES
366
13.4.1
N-PROPIONYLATED
PSA
CONJUGATE
VACCINE
366
13.4.2
IMMUNOLOGY
OF
NPR
PSA
368
13.4.3
PROTECTIVE
EPITOPE
MIMICKED
BY
NPR
PSA
370
13.4.4
SAFETY
CONCERNS
370
13.5
CANCER
VACCINES
371
13.5.1
PSA
ON
HUMAN
CELLS
371
13.5.2
POTENTIAL
OF
NPR
PSA
AS
A
CANCER
VACCINE
373
13.6
ACKNOWLEDGEMENTS
375
13.7
REFERENCES
375
14
SYNTHETIC
CARBOHYDRATE-BASED
VACCINES
381
STACY
J.
KEDING
AND
SAMUEL
J.
DANISHEFSKY
14.1
INTRODUCTION
381
14.2
CANCER
VACCINES
382
14.2.1
CARRIER
PROTEINS
384
14.2.2
LIPID
CARRIERS
392
14.2.3
T-CELL
EPITOPES
394
14.2.4
DENDRIMERS
396
14.3
BACTERIAL
POLYSACCHARIDE
VACCINES
397
14.4
SYNTHETIC
PARASITIC
POLYSACCHARIDE
CONJUGATE
VACCINE
402
14.5
CONCLUSIONS
403
14.6
REFERENCES
403
15
CHEMISTRY,
BIOCHEMISTRY,
AND
PHARMACEUTICAL
POTENTIALS
OF
GLYCOSAMINOGLYCANS
AND
RELATED
SACCHARIDES
407
TASNEEM
ISLAM
AND
ROBERT
J.
LINHARDT
15.1
INTRODUCTION
407
15.1.1
BIOLOGICAL
ACTIVITIES
408
15.1.2
HEPARIN
AND
HEPARAN
SULFATE
409
15.1.2.1
STRUCTURE
AND
PROPERTIES
409
15.1.2.2
BIOSYNTHESIS
AND
BIOLOGICAL
FUNCTIONS
410
15.1.2.3
APPLICATIONS
OF
HEPARIN
AND
HEPARAN
SULFATE
411
15.2
DERMATAN
AND
CHONDROITIN
SULFATES
417
15.2.1
STRUCTURE
AND
BIOLOGICAL
ROLE
417
15.2.2
THERAPEUTIC
APPLICATIONS
418
15.2.2.1
DERMATAN
SULFATE
418
XII
I
CONTENTS
15.2.2.2
15.3
15.3.1
15.3.2
15.3.3
15.3.3.1
15.3.3.2
15.4
15.4.1
15.4.2
15.4.2.1
15.4.2.2
15.4.3
15.4.3.1
15.5
15.5.1
15.5.2
15.5.3
15.5.4
15.5.5
15.5.6
15.5.7
15.5.7.1
15.5.7.2
15.6
15.6.1
15.6.2
CHONDROITIN
SULFATES
419
HYALURONAN
419
STRUCTURE
AND
PROPERTIES
419
TISSUE
DISTRIBUTION
AND
BIOSYNTHESIS
420
FUNCTIONS
AND
APPLICATIONS
421
MEDICAL
APPLICATIONS
422
HYALURONIC
ACID
BIOMATERIALS
423
KERATAN
SULFATE
423
STRUCTURE
AND
DISTRIBUTION
423
CHEMISTRY
AND
BIOSYNTHESIS
OF
LINKAGE
REGIONS
424
KERATAN
SULFATE
ON
CARTILAGE
PROTEOGLYCANS
424
KERATAN
SULFATE
ON
CORNEAL
PROTEOGLYCANS
424
BIOLOGICAL
ROLES
OF
KERATAN
SULFATE
425
ROLE
OF
KS
IN
MACULAR
CORNEAL
DYSTROPHY
425
OTHER
ACIDIC
POLYSACCHARIDES
425
ACHARAN
SULFATE
425
FUCOIDINS
426
CARRAGEENANS
427
SULFATED
CHITINS
427
DEXTRAN
SULFATE
427
ALGINATES
428
FULLY
SYNTHETIC
SULFATED
MOLECULES
428
POLYMERS
428
SMALL
SULFONATED
MOLECULES
428
PHARMACEUTICAL
POTENTIAL
AND
CHALLENGES
430
GAG-BASED
AGENTS
ARE
HETEROGENOUS
431
GAG-BASED
AGENTS
AND
SULFONATED
ANALOGUES
HAVE
LOW
BIOAVAILABILITY
431
15.6.3
15.6.4
15.7
15.8
GAGS
HAVE
A
MYRIAD
OF
BIOLOGICAL
ACTIVITIES
432
CARBOHYDRATE-BASED
DRUGS
ARE
EXPENSIVE
AND
DIFFICULT
TO
PREPARE
432
CONCLUSION
432
REFERENCES
433
16
A
NEW
GENERATION
OF
ANTITHROMBOTICS
BASED
ON
SYNTHETIC
OLIGOSACCHARIDES
441
MAURICE
PETITOU
AND
JEAN-MARC
HERBERT
16.1
16.2
16.2.1
INTRODUCTION
441
HEPARIN
AND
ITS
MECHANISM
OF
ACTION
AS
AN
ANTITHROMBOTIC
AGENT
442
HEPARIN,
A
COMPLEX
POLYSACCHARIDE
WITH
BLOOD
ANTICOAGULANT
PROPERTIES
442
16.2.2
16.2.3
16.2.4
16.3
WHICH
COAGULATION
FACTOR
MUST
BE
INHIBITED?
442
THE
STRUCTURE
OF
HEPARIN
IN
RELATION
TO
ANTITHROMBIN
ACTIVATION
444
THE
LIMITATIONS
OF
HEPARIN
445
SYNTHETIC
PENTASACCHARIDES,
SELECTIVE
FACTOR
XA
INHIBITORS,
ARE
ANTITHROMBOTIC
AGENTS
446
CONTENTS
I
XIII
16.3.1
NEW
SYNTHETIC
OLIGOSACCHARIDES
REQUIRED
IN
ORDER
TO
VALIDATE
A
PHARMACOLOGICAL
HYPOTHESIS
446
16.3.2
A
STRATEGY
FOR
THE
SYNTHESIS
OF
AN
ACTIVE
PENTASACCHARIDE
446
16.3.3
A
STRATEGY
FOR
THE
SYNTHESIS
OF
THE
FIRST
PENTASACCHARIDE
448
16.3.4
ACTIVATION
OF
ANTITHROMBIN:
STRUCTURE/ACTIVITY
RELATIONSHIP
449
16.3.5
CLINICAL
TRIALS
RESULTS
449
16.3.6
THE
SECOND
GENERATION
OF
ANTITHROMBOTIC
PENTASACCHARIDES
451
16.4
SYNTHETIC
THROMBIN-INHIBITING
OLIGOSACCHARIDES:
THE
NEXT
GENERATION?
452
16.4.1
FIRST
APPROACH:
OLIGOMERIZATION
OF
A
DISACCHARIDE
452
16.4.2
SECOND
APPROACH:
MOLECULES
CONTAINING
TWO
IDENTIFIED
DOMAINS
453
16.4.3
INTRODUCTION
OF
A
NEUTRAL
DOMAIN
454
16.5
THE
MECHANISM
OF
ANTITHROMBIN
ACTIVATION
BY
SYNTHETIC
OLIGOSACCHARIDES
456
16.6
CONCLUSION
AND
PERSPECTIVES
456
16.7
REFERENCES
457
VOLUME
2
17
SEQUENCING
OF
OLIGOSACCHARIDES
AND
GLYCOPROTEINS
461
STUART
M.
HASLAM,
KAY-HOOI
KHOO,
AND
ANNE
DELL
17.1
MASS
SPECTROMETRY
462
17.1.1
EI-,
FAB-,
AND
MALDI-MS
462
17.1.2
ES,
NANOES,
AND
LC-MS
464
17.1.3
MS/MS
AND
MASS
ANALYZERS
465
17.2
MS-BASED
SEQUENCING
STRATEGIES
466
17.2.1
CHEMICAL
DERIVATIZATION
467
17.2.2
MS/MS
FRAGMENTATION
PATTERNS
467
17.2.3
PERMETHYLATION
AND
SEQUENCE
ASSIGNMENT
FROM
FRAGMENT
IONS
468
17.3
GLYCAN
SEQUENCING
AND
STRUCTURAL
DETERMINATION
-
A
CASE
STUDY
470
17.3.1
GC-MS
SUGAR
ANALYSIS
471
17.3.2
GLYCAN
DERIVATIZATION
471
17.3.3
FAB-MS
OF
THE
DEUTEROREDUCED
PERMETHYLATED
HSP
SAMPLE
473
17.3.4
ES-MS/MS
473
17.3.5
LINKAGE
ANALYSIS
474
17.3.6
CHEMICAL
HYDROLYSIS
474
17.3.7
EXO-GLYCOSIDASE
DIGESTION
474
17.4
MAMMALIAN
GLYCOMICS
475
17.5
SOME
SPECIAL
CASE
STRATEGIES
477
17.6
REFERENCES
481
XIV
CONTENTS
18
PREPARATION
OF
HETEROCYCLIC
2-DEOXYSTREPTAMINE
AMINOGLYCOSIDE
ANALOGUES
AND
CHARACTERIZATION
OF
THEIR
INTERACTION
WITH
RNAS
BY
USE
OF
ELECTROSPRAY
IONIZATION
MASS
SPECTROMETRY
483
RICHARD
H.
GRIFFEY,
STEVEN
A.
HOFSTADLER,
AND
ERIC
E.
SWAYZE
18.1
18.1.1
18.1.2
18.1.3
18.2
18.2.1
18.2.2
18.2.3
18.3
INTRODUCTION
483
RNA
AS
A
TARGET
483
FUNCTIONAL
RNA
SUBDOMAINS
483
AMINOGLYCOSIDES
ARE
A
PRIVILEGED
CLASS
OF
RNA
LIGANDS
484
ESI-MS
FOR
CHARACTERIZATION
OF
AMINOGLYCOSIDE-RNA
INTERACTIONS
484
AMINOGLYCOSIDE-16S
AND
18S
A
SITE
RNA
MODELS
484
NEOMYCIN
AND
TAR
RNA
489
INTERIM
SUMMARY
490
PREPARATION
OF
HETEROCYCLIC
2-DEOXYSTREPTAMINES
AND
BINDING
TO
A
16S
A
SITE
RNA
MODEL
490
,
18.3.1
18.3.2
18.3.3
18.4
4-SUBSTITUTED
2-DEOXYSTREPTAMINE
DERIVATIVES
491
16S
RRNA
BINDING
AFFINITY
STUDY
IN
AN
ESI-MS
ASSAY
493
ISOLATION
OF
SUGAR
RING
FRAGMENTS
FROM
NEOMYCIN
494
PREPARATION,
BINDING,
AND
BIOLOGICAL
ACTIVITY
OF
SUBSTITUTED
PAROMOMYCIN
DERIVATIVES
495
18.4.1
SYNTHESIS
OF
RACEMIC
A
RING-SUBSTITUTED
PAROMOMYCIN
ANALOGUES
495
18.4.2
18.5
18.6
18.7
SYNTHESIS
OF
CHIRAL
A
RING-SUBSTITUTED
PAROMOMYCIN
ANALOGUES
496
FUTURE
PROSPECTS
498
ACKNOWLEDGEMENTS
498
REFERENCES
498
19
GLYCOSYLATION
ANALYSIS
OF
A
RECOMBINANT
P-SELECTIN
ANTAGONIST
BY
HIGH-PH
ANION-EXCHANGE
CHROMATOGRAPHY
WITH
PULSED
ELECTROCHEMICAL
DETECTION
(HPAEC/PED)
501
MARK
R.
HARDY
AND
RICHARD
J.
CORNELL
19.1
19.2
19.3
19.3.1
19.4
19.4.1
19.4.2
19.4.3
19.5
19.5.1
INTRODUCTION
501
USE
OF
HPAEC/PED
IN
THE
DEVELOPMENT
OF
BIOPHARMACEUTICALS
502
BIOLOGY
OF
P-SELECTIN
503
STRUCTURES
OF
PSGL-1
AND
RPSGL-IG
503
HPAEC/PED
AS
AN
ADJUNCT
TO
RPSGL-IG
PROCESS
DEVELOPMENT
504
MATERIALS
AND
METHODS
504
HPAEC/PED
O-LINKED
OLIGOSACCHARIDE
PROFILE
ANALYSIS
506
N-LINKED
OLIGOSACCHARIDE
PROFILE
ANALYSIS
507
RESULTS
AND
DISCUSSION
508
HPAEC/PED
OLIGOSACCHARIDE
PROFILE
ANALYSIS
OF
A
DEVELOPMENTAL
BATCH
OFRPSGL-IG
508
19.5.2
19.5.3
19.5.4
REPEATABILITY
OF
THE
O-LINKED
OLIGOSACCHARIDE
PROFILE
METHOD
510
O-GLYCOSYLATION
OF
RPSGL-IG
EXPRESSED
BY
DIFFERENT
CELL
LINES
510
N-GLYCOSYLATION
OF
RPSGL-IG
515
CONTENTS
I
XV
19.6
SUMMARY
515
19.7
ACKNOWLEDGEMENTS
516
19.8
REFERENCES
516
20
ANALYTICAL
TECHNIQUES
FOR
THE
CHARACTERIZATION
AND
SEQUENCING
OF
GLYCOSAMINOGLYCANS
517
RAM
SASISEKHARAN,
ZACHARY
SHRIVER,
MALLIK
SUNDARAM,
AND
GANESH
VENKATARAMAN
20.1
INTRODUCTION
TO
GAG
LINEAR
COMPLEX
POLYSACCHARIDES
517
20.2
DEPOLYMERIZATION
OF
NASCENT
GAG
CHAINS
521
20.2.1
ENZYMES
THAT
DEGRADE
GAGS
521
20.2.2
CHEMICAL
METHODS
FOR
DEGRADING
GAG
OLIGOSACCHARIDES
524
20.3
DETECTION
OF
GAG
OLIGOSACCHARIDES
525
20.3.1
A
4,5
BOND
FORMATION
AND
UV
DETECTION
525
20.3.2
FLUORESCENT
TAGGING
526
20.3.3
METABOLIC
LABELING
526
20.4
ANALYTICAL
TOOLS
USED
IN
THE
STRUCTURAL
CHARACTERIZATION
OF
GAGS
527
20.4.1
HIGH
PRESSURE
LIQUID
CHROMATOGRAPHY
527
20.4.1.1
AMINO-BONDED
SILICA
528
20.4.1.2
HIGH-PERFORMANCE
GEL
PERMEATION
528
20.4.1.3
WEAK
AND
STRONG
ANION
EXCHANGE
528
20.4.1.4
PELLICULAR
ANION
EXCHANGE
529
20.4.1.5
IP-RPHPLC
529
20.4.1.6
SEQUENCING
GAGS
I:
HPLC
METHODS
529
20.4.2
POLYACRYLAMIDE
GEL
ELECTROPHORESIS
530
20.4.2.1
SEQUENCING
GAGS
II:
PAGE
METHODS
530
20.4.3
CAPILLARY
ELECTROPHORESIS
530
20.4.4
NMR
SPECTROSCOPY
532
20.4.5
MASS
SPECTROMETRY
533
20.4.5.1
SEQUENCING
GAGS
III:
MASS
SPECTROMETRIC
METHODOLOGIES
536
20.4.6
OLIGOSACCHARIDE
ARRAY
TECHNOLOGIES
536
20.5
FUTURE
DIRECTIONS
536
20.6
ACKNOWLEDGEMENTS
537
20.7
REFERENCES
537
21
THERMODYNAMIC
MODELS
OF
THE
MULTIVALENCY
EFFECT
541
PAVEL
I.
KITOV
AND
DAVID
R.
BUNDLE
21.1
INTRODUCTION
541
21.2
CONCEPT
OF
DISTRIBUTION
FREE
ENERGY
542
21.2.1
BINDING
ISOTHERM
542
21.2.2
COMPETITIVE
INHIBITION
ISOTHERM
544
21.3
MULTIVALENT
RECEPTOR
VS.
MONOVALENT
LIGAND
546
21.3.1
INTERIM
SUMMARY
549
21.4
MULTIVALENT
RECEPTOR
VS.
MULTIVALENT
LIGAND
551
21.5
TOPOLOGICAL
CLASSIFICATION
OF
MULTIVALENT
SYSTEMS
553
XVI
I
CONTENTS
21.5.1
21.5.2
21.5.3
21.5.4
21.6
INDIFFERENT
PRESENTATION
553
LINEAR
PRESENTATION
554
CIRCULAR
PRESENTATION
554
RADIAL
PRESENTATION
554
DETERMINATION
OF
MICROSCOPIC
BINDING
PARAMETERS
BY
MOLECULAR
MODELING
555
21.6.1
OPTIMIZATION
OF
THE
TETHER
IN
BIVALENT
P
K
-TRISACCHARIDE
LIGANDS
FOR
SHIGA-LIKE
TOXIN
557
21.7
DETERMINATION
OF
MICROSCOPIC
BINDING
PARAMETERS
FROM
BINDING
DATA
561
21.8
21.8.1
21.9
21.10
21.10.1
21.10.2
21.10.3
21.10.4
21.10.5
21.11
THERMODYNAMIC
ANALYSIS
OF
MULTIVALENT
INTERACTION
562
RADIALLY
ARRANGED
MULTIVALENT
LIGANDS
FOR
SHIGA-LIKE
TOXIN
565
CONCLUSIONS
570
MATHEMATICAL
APPENDIX
570
CALCULATION
OF
STATISTICAL
COEFFICIENTS
570
MULTIVALENT
RECEPTOR
AND
MONOVALENT
LIGAND
571
MULTIVALENT
BINDING
WITH
LINEAR
AND
CIRCULAR
TOPOLOGY
571
MULTIVALENT
BINDING
WITH
RADIAL
TOPOLOGY
572
DERIVATION
OF
EQ.
(24)
572
REFERENCES
573
22
SYNTHETIC
MULTIVALENT
CARBOHYDRATE
LIGANDS
AS
EFFECTORS
OR
INHIBITORS
OF
BIOLOGICAL
PROCESSES
575
LAURA
L.
KIESSLING,
JASON
K.
PONTRELLO,
AND
MICHAEL
C.
SCHUSTER
22.1
22.1.1
22.1.2
INTRODUCTION
575
MECHANISMS
OF
BINDING
OF
MULTIVALENT
LIGANDS
576
INVESTIGATING
THE
STRUCTURE/FUNCTION
RELATIONSHIP
OF
A
SERIES
OF
LIGAND
CLASSES
577
22.2
22.2.1
22.2.1.1
22.2.1.2
MULTIVALENT
CARBOHYDRATE
LIGANDS
AS
INHIBITORS
581
MULTIVALENCY
WITH
AB
5
TOXINS
581
BUNDLE
'
S
DECAVALENT
LIGAND
FOR
THE
E.
COLI
SHIGA-LIKE
TOXIN
582
FARIS
PENTAVALENT
LIGANDS
FOR
CHOLERA
TOXIN
AND
THE
E.
COLI
HEAT-LABILE
ENTEROTOXIN
584
22.2.2
22.2.2.1
MULTIVALENCY
IN
ANTI-ADHESIVES
587
LOW
MOLECULAR
WEIGHT
MULTIVALENT
CARBOHYDRATE
INHIBITORS
OF
BACTERIAL
ADHESION
587
22.2.2.2
22.2.3
POLYMERIC
MULTIVALENT
CARBOHYDRATE
INHIBITORS
OF
INFLUENZA
VIRUS
592
MULTIVALENT
CARBOHYDRATE
LIGANDS
AS
INHIBITORS
OF
IMMUNE
RESPONSES
595
22.3
22.3.1
22.3.2
22.3.3
22.3.4
22.3.5
MULTIVALENT
CARBOHYDRATE
LIGANDS
AS
EFFECTORS
596
LOW
MOLECULAR
WEIGHT
MULTIVALENT
EFFECTORS
597
MULTIVALENCY
IN
TARGETING
STRATEGIES
599
MULTIVALENT
BACTERIAL
CHEMOATTRACTANTS
600
MULTIVALENT
LIGAND-MEDIATED
CELL
AGGREGATION
602
MULTIVALENT
LIGANDS
AND
THE
SELECTINS
603
CONTENTS
XVII
22.4
22.5
CONCLUSIONS
605
REFERENCES
605
23
CLYCOSYLTRANSFERASE
INHIBITORS
609
KARL-HEINZ
JUNG
AND
RICHARD
R.
SCHMIDT
23.1
23.2
23.2.1
23.2.1.1
23.2.1.2
23.2.1.3
23.2.1.4
23.2.1.5
23.2.2
23.2.2.1
23.2.2.2
23.3
23.3.1
23.3.2
23.4
23.5
23.6
INTRODUCTION
609
GLYCOSYLTRANSFERASES
UTILIZING
NDP-SUGAR
DONORS
610
INVERTING
GLYCOSYLTRANSFERASES
610
/1-GLUCOSYLTRANSFERASES
611
//-GALACTOSYL
TRANSFERASES
616
/I-N-ACETYLGLUCOSAMINYLTRANSFERASES
620
A-FUCOSYLTRANSFERASES
625
/I-GLUCURONOSYLTRANSFERASES
632
RETAINING
GLYCOSYLTRANSFERASES
636
A-GALACTOSYLTRANSFERASES
637
A-N-ACETYLGALACTOSAMINYLTRANSFERASES
640
GLYCOSYLTRANSFERASES
UTILIZING
NMP-SUGAR
DONORS
641
A(2-6)SIALYLTRANSFERASES
641
A(2-3)SIALYLTRANSFERASES
AND
A(2-8)SIALYLTRANSFERASES
647
BISUBSTRATE
ANALOGUES
AS
INHIBITORS
648
CONCLUSION
653
REFERENCES
654
24
RNA-AMINOGLYCOSIDE
INTERACTIONS
661
HAIM
WEIZMAN
AND
YITZHAK
TOR
24.1
24.2
24.3
24.4
24.5
24.6
24.7
24.8
24.9
24.10
RNA
AS
AN
EMERGING
THERAPEUTIC
TARGET
661
AMINOGLYCOSIDE
ANTIBIOTICS:
PAST
AND
PRESENT
664
AMINOGLYCOSIDES
AS
RNA
BINDERS
666
IDENTIFYING
RNA
TARGETS
AND
DEVELOPING
BINDING
ASSAYS
670
DIMERIC
AMINOGLYCOSIDES
673
AMINOGLYCOSIDE-INTERCALATOR
CONJUGATES
675
GUANIDINOGLYCOSIDES
677
SUMMARY
AND
OUTLOOK
679
ACKNOWLEDGEMENTS
680
REFERENCES
680
25
GLYCOSYLATED
NATURAL
PRODUCTS
685
JON
S.
THORSON
AND
THOMAS
VOGT
25.1
25.2
25.2.1
25.2.1.1
25.2.1.2
25.2.1.3
25.2.1.4
INTRODUCTION
685
A
SUMMARY
OF
BIOACTIVE
GLYCOSYLATED
SECONDARY
METABOLITES
686
AGENTS
THAT
INTERACT
WITH
DNA
686
ENEDIYNES
686
BLEOMYCINS
688
DIAZOBENZOFLUORENES
689
ANTHRACYDINES
689
XVIII
I
CONTENTS
25.2.1.5
25.2.1.6
25.2.2
25.2.2.1
25.2.2.2
25.2.2.3
25.2.2.4
25.2.3
25.2.3.1
25.2.3.2
25.2.3.3
25.2.4
25.2.4.1
25.2.4.2
25.2.4.3
25.2.4.4
25.2.4.5
25.2.4.6
25.2.4.7
25.2.4.8
25.2.4.9
25.2.4.10
25.2.4.11
25.2.5
25.2.5.1
25.2.5.2
25.2.5.3
25.3
25.4
PLURAMYCINS
689
AUREOLIC
ACIDS
690
AGENTS
THAT
INTERACT
WITH
RNA
692
ORTHOSOMYCINS
692
MACROLIDES
692
AMINOGLYCOSIDES
694
AMICETINS
695
AGENTS
THAT
INTERACT
WITH
CELL
WALLS
AND
CELL
MEMBRANES
695
NON-RIBOSOMAL
PEPTIDES
695
POLYENES
697
SACCHAROMICINS
699
AGENTS
THAT
INTERACT
WITH
PROTEINS
699
INDOLOCARBAZOLES
699
COUMARINS
699
BENZOISOCHROMANEQUINONES
701
AVERMECTINS
701
ANGUCYCLINES
701
CARDIAC
GLYCOSIDES
702
LIGNANS
703
ANTHRAQUINONE
GLYCOSIDES
703
GINSENOSIDES
704
GLYCOALKALOIDS
704
GLUCOSINOLATES
705
AGENTS
THAT
INTERACT
WITH
OTHER
(OR
UNDEFINED)
TARGETS
706
PLANT
PHENOLICS
706
MONO
AND
TRITERPENOID
GLYCOSIDES
707
PLANT
POLYMERIC
NATURAL
GLYCOSIDES
707
CONCLUSIONS
707
REFERENCES
707
26
NOVEL
ENZYMATIC
MECHANISMS
IN
THE
BIOSYNTHESIS
OF
UNUSUAL
SUGARS
713
ALEXANDER
WONG,
XUEMEI
HE,
AND
HUNG-WEN
LIU
26.1
26.2
26.2.1
INTRODUCTION
713
BIOSYNTHESIS
OF
DEOXYSUGARS
714
E
O
D-CATALYZED
C-0
BOND-CLEAVAGE
AT
THE
C-6
POSITION
IN
THE
BIOSYNTHESIS
OF
6-DEOXYHEXOSE
715
26.2.1.1
26.2.1.2
26.2.2
CATALYTIC
MECHANISM
OF
E
O
J
715
STEREOCHEMICAL
COURSE
OF
E
OD
-CATALYZED
REACTIONS
716
EI
AND
E
3
-CATALYZED
C-O
BOND-CLEAVAGE
AT
THE
C-3
POSITION
IN
THE
BIOSYNTHESIS
OF
ASCARYLOSE
717
26.2.2.1
CATALYTIC
PROPERTIES
OF
CDP-6-DEOXY-L-THREO-D-GLYCERO-4-HEXULOSE
3-DEHYDRASE
(E
T
)
718
26.2.2.2
CATALYTIC
PROPERTIES
OF
CDP-6-DEOXY-L-THREO-D-GLYCERO-4-HEXULOSE
3-DEHYDRASE
REDUCTASE
(E
3
)
719
26.2.2.3
FORMATION
OF
RADICAL
INTERMEDIATES
DURING
E
3
AND
E
3
CATALYSIS
719
CONTENTS
I
XIX
26.2.3
TYLX3
AND
TYLCL-CATALYZED
C-0
BOND-CLEAVAGE
AT
THE
C-2
POSITION
IN
THE
BIOSYNTHESIS
OF
MYCAROSE
720
26.2.3.1
BIOCHEMICAL
CHARACTERIZATION
OF
ENZYMES
INVOLVED
IN
C-2
DEOXYGENATION
721
26.2.3.2
MECHANISM
OF
C-2
DEOXYGENATION
721
26.2.4
DESI
AND
DESII-CATALYZED
C-0
BOND-CLEAVAGE
AT
THE
C-4
POSITION
IN
THE
BIOSYNTHESIS
OF
DESOSAMINE
722
26.2.4.1
GENETIC
DISRUPTION
OF
DESI
AND
DESII
GENES
723
26.2.4.2
PROPOSED
MECHANISMS
FOR
C-4
DEOXYGENATION
723
26.3
BIOSYNTHESIS
OF
AMINOSUGARS
725
26.3.1
C-N
BOND-FORMATION
BY
GLMS-CATALYZED
TRANSAMIDATION
IN
THE
BIOSYNTHESIS
OF
GLUCOSAMINE-6-PHOSPHATE
727
26.3.1.1
CATALYTIC
PROPERTIES
OF
GLUCOSAMINE-6-PHOSPHATE
SYNTHETASE
727
26.3.1.2
THE
GLUTAMINASE
ACTIVITY
OF
GLUCOSAMINE-6-PHOSPHATE
SYNTHETASE
727
26.3.1.3
THE
SYNTHETASE
ACTIVITY
OF
GLUCOSAMINE-6-PHOSPHATE
SYNTHETASE
728
26.3.2
C-N
BOND
FORMATION
BY
TYLB-CATALYZED
TRANSAMINATION
IN
THE
BIOSYNTHESIS
OF
MYCAMINOSE
729
26.4
BIOSYNTHESIS
OF
BRANCHED-CHAIN
SUGARS
730
26.4.1
YERE
AND
YERF-CATALYZED
TWO-CARBON
BRANCHED-CHAIN
ATTACHMENT
IN
THE
BIOSYNTHESIS
OF
YERSINIOSE
A
731
26.4.1.1
BIOCHEMICAL
PROPERTIES
AND
CATALYTIC
MECHANISM
OF
YERE
731
26.4.1.2
BIOCHEMICAL
PROPERTIES
OF
YERF
732
26.4.2
TYLC3-CATALYZED
ONE-CARBON
BRANCHED-CHAIN
ATTACHMENT
IN
THE
BIOSYNTHESIS
OF
MYCAROSE
732
26.4.2.1
BIOCHEMICAL
PROPERTIES
AND
CATALYTIC
MECHANISM
OF
TYLC3
733
26.5
EPIMERIZATION
REACTIONS
734
26.5.1
UDP-N-ACETYLGLUCOSAMINE
2-EPIMERASE-CATALYZED
C-2
EPIMERIZATION
IN
THE
BIOSYNTHESIS
OF
N-ACETYLMANNOSAMINE
734
26.5.1.1
CATALYTIC
PROPERTIES
OF
UDP-N-ACETYLGLUCOSAMINE
2-EPIMERASE
734
26.5.1.2
MECHANISM
OF
C-2
EPIMERIZATION
735
26.5.2
CDP-TYVELOSE
2-EPIMERASE-CATALYZED
C-2
EPIMERIZATION
IN
THE
BIOSYNTHESIS
OF
TYVELOSE
735
26.5.2.1
BIOCHEMICAL
PROPERTIES
OF
CDP-TYVELOSE
2-EPIMERASE
736
26.5.2.2
POSSIBLE
MECHANISMS
FOR
C-2
EPIMERIZATION
737
26.5.2.3
DISTINGUISHING
BETWEEN
MECHANISMS
INVOLVING
C-2
OR
C-4
OXIDA
TION
737
26.6
REARRANGEMENT
OF
HEXOSE
SKELETONS:
UDP-GALACTOPYRANOSE
MUTASE-CATALYZED
BIOSYNTHESIS
OF
GALACTOFURANOSE
738
26.6.1
CATALYTIC
PROPERTIES
OF
UDP-GALACTOPYRANOSE
MUTASE
738
26.6.2
MECHANISM
OF
RING
CONTRACTION
739
26.7
SUMMARY
740
XX
CONTENTS
26.8
26.9
ACKNOWLEDGEMENTS
741
REFERENCES
741
27
NEOGLYCOLIPIDS:
IDENTIFICATION
OF
FUNCTIONAL
CARBOHYDRATE
EPITOPES
747
TEN
FEIZI,
ALEXANDER
M.
LAWSON,
AND
WENGANG
CHAI
27.1
27.2
27.3
27.4
27.4.1
27.4.2
27.4.3
27.5
27.6
27.7
27.8
RATIONALE
FOR
DEVELOPING
NEOGLYCOLIPIDS
AS
OLIGOSACCHARIDE
PROBES
747
THE
FIRST
AND
SECOND
GENERATION
NEOGLYCOLIPIDS
749
MASS
SPECTROMETRY
OF
NEOGLYCOLIPIDS
750
SCOPE
OF
THE
NEOGLYCOLIPID
TECHNOLOGY
752
NOVEL
SULFATED
LIGANDS
FOR
THE
SELECTINS
752
NOVEL
CLASS
OF
O-GLYCANS
(O-MANNOSYL)
IN
THE
BRAIN
754
UNIQUE
TETRASACCHARIDE
SEQUENCE
ON
HEPARAN
SULFATE
755
OLIGOSACCHARIDE
MICROARRAYS
755
SUMMARY
AND
PERSPECTIVES
757
ACKNOWLEDGEMENT
757
REFERENCES
757
28
A
PREAMBLE
TO
AGLYCONE
RECONSTRUCTION
FOR
MEMBRANE-PRESENTED
GLYCOLIPID
MIMICS
761
MURUGESAPILLAI
MYLVAGANAM
AND
CLIFFORD
A.
LINGWOOD
28.1
28.2
28.3
INTRODUCTION
761
THE
ROLE
OF
CERAMIDE
SUBTYPE
COMPOSITION
762
EFFECTS
OF
CERAMIDE
SUBTYPE
COMPOSITION
IN
THE
BINDING
OF
GB
3
CER
TO
VEROTOXINS
764
28.4
HYPOTHESIS
REGARDING
LIPID
REPLACEMENT
STRUCTURAL
MOTIFS
(LRSMS)
766
28.5
EFFECT
OF
REPLACEMENT
OF
GSL
FATTY
ACYL
CHAINS
WITH
RIGID,
NON-PLANAR
HYDROPHOBIC
GROUPS
768
28.6
ADA-GBJCER,
A
FUNCTIONAL
MIMIC
OF
MEMBRANE
PRESENTED
GB
3
CER
FOR
VT
BINDING
769
28.7
CERAMIDE
SUBTYPE-DEPENDENT
BINDING
OF
HEAT
SHOCK
PROTEIN
HSP70
TO
SULFOGALACTOSYL
CERAMIDE
772
28.8
ADAMANTYL-ACYL
CERAMIDE
IS
A
FUNCTIONAL
REPLACEMENT
FOR
A
CERAMIDE-CHOLESTEROL
COMPOSITION:
A
STUDY
WITH
HIV
COAT
PROTEIN
GPL20
775
28.9
28.10
ACKNOWLEDGEMENT
777
REFERENCES
777
29
SMALL
MOLECULE
INHIBITORS
OF
THE
SULFOTRANSFERASES
781
DAWN
E.
VERDUGO,
LARS
C.
PEDERSEN,
AND
CAROLYN
R.
BERTOZZI
29.1
29.2
29.2.1
29.2.2
29.2.3
INTRODUCTION:
SULFOTRANSFERASES
AND
THE
BIOLOGY
OF
SULFATION
781
EST
AS
A
MODEL
ST
FOR
INHIBITOR
DESIGN
783
INHIBITORS
OF
EST
TARGETED
TOWARD
THE
PAPS
BINDING
SITE
784
A
BISUBSTRATE
ANALOGUE
APPROACH
TO
EST
INHIBITION
788
DISCOVERY
OF
EST
INHIBITORS
FROM
A
LIBRARY
OF
PAP
ANALOGUES
789
CONTENTS
I
XXI
29.2.4
INHIBITION
OF
EST
BY
DIETARY
AGENTS
AND
ENVIRONMENTAL
TOXINS
791
29.3
INHIBITION
OF
REPRESENTATIVE
GOLGI-RESIDENT
SULFOTRANSFERASES:
GST-2,
GST-3,
AND
TPST-2
792
29.3.1
HETEROCYCLIC
INHIBITORS
OF
GST-2
AND
GST-3
792
29.3.2
TETHERED
INHIBITORS
OF
TPST-2
793
29.4
ASSAYS
FOR
HIGH-THROUGHPUT
SCREENING
OF
STS
794
29.4.1
A
CONTINUOUS
ST
ASSAY
794
29.4.2
IMMOBILIZED
ENZYME
MASS
SPECTROMETRY
(IEMS)
ASSAY
795
29.4.3
A
96-WELL
DIRECT
CAPTURE
'
DOT-BLOT
1
ASSAY
FOR
CARBOHYDRATE
STS
795
29.5
NEW
DIRECTIONS
IN
INHIBITOR
DISCOVERY
796
29.6
CONCLUSIONS
796
29.7
ACKNOWLEDGEMENTS
796
29.8
REFERENCES
797
30
CARBOHYDRATE-BASED
TREATMENT
OF
CANCER
METASTASIS
803
REIJI
KANNAGI
30.1
IMPLICATION
OF
CARBOHYDRATE
DETERMINANTS
IN
CANCER
METASTASIS
803
30.1.1
DISTANT
HEMATOGENOUS
METASTASIS
OF
CANCER
CELLS
803
30.1.2
MULTIPLE
ORGAN
INFILTRATION
OF
LEUKEMIC
CELLS
806
30.1.3
LYMPH
NODE
INFILTRATION
MEDIATED
BY
L-SELECTIN
807
30.1.4
OTHER
CARBOHYDRATE
DETERMINANTS
INVOLVED
IN
DISTANT
METASTASIS
807
30.2
TUMOR
ANGIOGENESIS
AND
CANCER-ENDOTHELIAL
INTERACTION
808
30.2.1
POSSIBLE
INVOLVEMENT
OF
SELECTIN-MEDIATED
CELL
ADHESION
IN
TUMOR
ANGIOGENESIS
808
30.2.2
ROLES
OF
HUMORAL
FACTORS
AND
CELL
ADHESION
MOLECULES
IN
TUMOR
ANGIOGENESIS
809
30.3
USE
OF
MONOCLONAL
ANTIBODIES
FOR
INHIBITION
OF
CANCER
CELL-ENDOTHELIAL
INTERACTION
809
30.3.1
DIVERSITY
OF
SELECTIN
LIGAND
EXPRESSION
ON
CANCER
CELLS
809
30.3.2
INTERNALLY
FUCOSYLATED
LIGANDS
FOR
SELECTINS
810
30.3.3
SULFATED
LIGANDS
FOR
SELECTINS
811
30.3.4
O-ACETYLATION
AND
OTHER
SIALIC
ACID
MODIFICATIONS
IN
CARBOHYDRATE
LIGANDS
812
30.4
INHIBITORS
OF
SELECTIN-MEDIATED
CELL
ADHESION
812
30.4.1
USE
OF
CARBOHYDRATE
DERIVATIVES
812
30.4.2
USE
OF
PEPTIDE
MIMETICS
813
30.5
REGULATION
OF
SELECTIN
EXPRESSION
ON
ENDOTHELIAL
CELLS
814
30.5.1
ENHANCED
E-SELECTIN
EXPRESSION
ON
VASCULAR
BEDS
IN
CANCER
PATIENTS
814
30.5.2
FACTORS
AFFECTING
ENDOTHELIAL
E-SELECTIN
EXPRESSION
IN
PATIENTS
WITH
CANCERS
815
30.5.3
CHEMOPROPHYLAXIS
OF
CANCER
METASTASIS
815
30.6
ENHANCED
EXPRESSION
OF
SIALYL
LE
X
AND
SIALYL
LE
A
IN
MALIGNANT
CELLS
AND
ITS
MODULATION
816
XXII
CONTENTS
30.6.1
FUCOSYLTRANSFERASES
INVOLVED
IN
SIALYL
LE
A
AND
SIALYL
LE
X
SYNTHESIS
AND
ANTISENSE
GENE
THERAPY
816
30.6.2
THERAPY
TARGETING
TRANSCRIPTIONAL
REGULATION
OF
FUCOSYLTRANSFERASES
VII
AND
IV
IN
CANCER
AND
LEUKEMIA
817
30.6.3
30.6.4
CANCER-ASSOCIATED
ALTERATION
OF
SIALYLTRANSFERASE
ISOENZYMES
818
SIALYLTRANSFERASE
AND
THE
CONCEPT
OF
CANCER-ASSOCIATED
"
INCOMPLETE
SYNTHESIS
"
OF
CARBOHYDRATE
DETERMINANTS
820
30.6.5
SULFOTRANSFERASE
AND
DIFFERENTIATION
THERAPY
OF
CANCER
WITH
HISTONE
DEACETYLASE
INHIBITORS
820
30.6.6
EFFECT
OF
SIALIDASES
AND
MEMBRANE
RECYCLING
ON
SIALYL
LE
X/A
EXPRESSION
IN
CANCER
822
30.6.7
SUBSTRATE
COMPETITION
WITH
A
AND
B-TRANSFERASES
AND
DNA
METHYLATION
822
30.6.8
ALTERED
CARBOHYDRATE
INTERMEDIATE
METABOLISM
AND
SIALYL
LE
X,/A
EXPRESSION
IN
CANCER
-
POSSIBLE
RELATION
TO
WARBURG
THEORY
823
30.7
REFERENCES
824
31
N-ACETYLNEURAMINIC
ACID
DERIVATIVES
AND
MIMETICS
AS
ANTI-INFLUENZA
AGENTS
831
ROBIN
THOMSON
AND
MARK
VON
ITZSTEIN
31.1
31.1.1
31.1.2
31.1.3
31.2
INTRODUCTION
831
INFLUENZA,
THE
DISEASE
831
THE
VIRUS
832
INFLUENZA
VIRUS
SIALIDASE
834
STRUCTURE-BASED
DESIGN
OF
INHIBITORS
OF
INFLUENZA
VIRUS
SIALIDASE
836
31.3
STRUCTURE
/ACTIVITY
RELATIONSHIP
STUDIES
OF
N-ACETYLNEURAMINIC
ACID-BASED
INFLUENZA
VIRUS
SIALIDASE
INHIBITORS
840
31.3.1
31.3.2
31.3.3
31.3.4
31.3.5
31.4
31.5
31.6
C-4
MODIFICATIONS
840
C-5
MODIFICATIONS
842
C-6
MODIFICATIONS
843
GLYCEROL
SIDE
CHAIN
MODIFICATIONS
845
GLYCEROL
SIDE
CHAIN
REPLACEMENT
850
CONCLUDING
REMARKS
856
ACKNOWLEDGEMENTS
856
REFERENCES
857
32
MODIFIED
AND
MODIFYING
SUGARS
AS
A
NEW
TOOL
FOR
THE
DEVELOPMENT
OF
THERAPEUTIC
AGENTS
-
THE
BIOCHEMICALLY
ENGINEERED
N-ACYL
SIDE
CHAIN
OF
SIALIC
ACID:
BIOLOGICAL
IMPLICATIONS
AND
POSSIBLE
USES
IN
MEDICINE
863
RUDIGER
HORSTKORTE,
OLIVER
T.
KEPPLER,
AND
WERNER
REUTTER
32.1
32.2
INTRODUCTION
863
N-ACYL
SIDE
CHAIN-MODIFIED
PRECURSORS
OF
SIALIC
ACID
865
CONTENTS
XXIII
32.2.1
BIOSYNTHETIC
ENGINEERING
OF
CELL
SURFACE
SIALIC
ACID
AS
A
POTENT
TOOL
FOR
STUDY
OF
VIRUS-RECEPTOR
INTERACTIONS
865
32.2.2
IMMUNOTARGETING
OF
TUMOR
CELLS
EXPRESSING
UNNATURAL
POLYSIALIC
ACIDS
868
32.2.3
32.2.4
32.2.4.1
32.2.4.2
32.3
32.4
32.5
32.6
ACTIVATION
OF
HUMAN
T-LYMPHOCYTES
BY
MANPROP
869
N-ACYL-MODIFIED
SIALIC
ACIDS
CAN
STIMULATE
NEURAL
CELLS
869
STIMULATION
OF
GLIAL
CELLS
869
STIMULATION
OF
NEURONS
870
OUTLOOK
871
ACKNOWLEDGEMENTS
872
ABBREVIATIONS
872
REFERENCES
872
33
MODIFIED
AND
MODIFYING
SUGARS
AS
A
NEW
TOOL
FOR
THE
DEVELOPMENT
OF
THERAPEUTIC
AGENTS
-
CLYCOSIDATED
PHOSPHOLIPIDS
AS
A
NEW
TYPE
OF
ANTIPROLIFERATIVE
AGENTS
875
KERSTIN
DANKER,
ANNETTE
FISCHER,
AND
WERNER
REUTTER
33.1
33.2
33.3
INTRODUCTION
875
STRUCTURES
OF
SYNTHETIC
GLYCOSIDATED
PHOSPHOLIPID
ANALOGUES
876
ANTIPROLIFERATIVE
EFFECT
AND
CYTOTOXICITY
OF
GLYCOSIDATED
PHOSPHOLIPID
ANALOGUES
IN
CELL
CULTURE
SYSTEMS
876
33.4
EFFECT
OF
GLYCOSIDATED
PHOSPHOLIPID
ANALOGUES
ON
CELL
MATRIX
ADHESION
878
33.5
33.6
33.7
33.8
MECHANISMS
OF
ACTION
879
OUTLOOK
AND
NEW
DEVELOPMENTS
880
ACKNOWLEDGEMENTS
881
REFERENCES
881
34
GLYCOSIDE
PRIMERS
AND
INHIBITORS
OF
GLYCOSYLATION
883
JILLIAN
R.
BROWN,
MARK
M.
FASTER,
AND
JEFFREY
D.
ESKO
34.1
34.2
34.3
34.4
34.5
34.6
34.7
INTRODUCTION
883
GLYCOSIDE-BASED
SUBSTRATES
883
GLYCOSIDE
PRIMERS
-
XYLOSIDES
884
OTHER
TYPES
OF
PRIMERS
885
GLYCOSIDES
AS
METABOLIC
DECOYS
888
ANALOGUES
890
REFERENCES
892
35
CARBOHYDRATE-BASED
DRUG
DISCOVERY
IN
THE
BATTLE
AGAINST
BACTERIAL
INFECTIONS:
NEW
OPPORTUNITIES
ARISING
FROM
PROGRAMMABLE
ONE-POT
OLIGOSACCHARIDE
SYNTHESIS
899
THOMAS
K.
RITTER
AND
CHI-HUEY
WONG
35.1
35.2
35.3
INTRODUCTION
899
CELL-SURFACE
CARBOHYDRATES
900
PEPTIDOGLYCAN
904
XXIV
CONTENTS
35.4
35.5
35.6
35.7
35.8
MACROLIDE
ANTIBIOTICS
913
AMINOGLYCOSIDES
917
PROGRAMMABLE
ONE-POT
OLIGOSACCHARIDE
SYNTHESIS
922
SUMMARY
927
REFERENCES
928
SUBJECT
INDEX
933 |
| any_adam_object | 1 |
| building | Verbundindex |
| bvnumber | BV017502707 |
| classification_rvk | VS 5350 |
| classification_tum | MED 920f CIT 840f CHE 893f CHE 850f |
| ctrlnum | (DE-599)BVBBV017502707 |
| discipline | Chemie / Pharmazie Chemie Chemie-Ingenieurwesen Medizin |
| format | Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>00000nam a2200000 ca4500</leader><controlfield tag="001">BV017502707</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20050707</controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">030917nuuuuuuuugw |||| 00||| eng d</controlfield><datafield tag="016" ind1="7" ind2=" "><subfield code="a">966548892</subfield><subfield code="2">DE-101</subfield></datafield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">3527306323</subfield><subfield code="9">3-527-30632-3</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV017502707</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakddb</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="044" ind1=" " ind2=" "><subfield code="a">gw</subfield><subfield code="c">DE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">VS 5350</subfield><subfield code="0">(DE-625)147687:253</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">MED 920f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">CIT 840f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">CHE 893f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">CHE 850f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Carbohydrate-based drug discovery</subfield><subfield code="c">Chi-Huey Wong (Ed.)</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Weinheim</subfield><subfield code="b">Wiley-VCH</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">Kohlenhydrate</subfield><subfield code="0">(DE-588)4164517-0</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Chemie</subfield><subfield code="0">(DE-588)4009816-3</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Arzneimittelforschung</subfield><subfield code="0">(DE-588)4003120-2</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Arzneimittelforschung</subfield><subfield code="0">(DE-588)4003120-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="1"><subfield code="a">Kohlenhydrate</subfield><subfield code="0">(DE-588)4164517-0</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="2"><subfield code="a">Chemie</subfield><subfield code="0">(DE-588)4009816-3</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wong, Chi-Huey</subfield><subfield code="e">Sonstige</subfield><subfield code="4">oth</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">DNB 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=012750688&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="943" ind1="1" ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-012750688</subfield></datafield></record></collection> |
| id | DE-604.BV017502707 |
| illustrated | Not Illustrated |
| indexdate | 2024-08-22T00:20:07Z |
| institution | BVB |
| isbn | 3527306323 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-012750688 |
| open_access_boolean | |
| publishDateSort | 0000 |
| publisher | Wiley-VCH |
| record_format | marc |
| spelling | Carbohydrate-based drug discovery Chi-Huey Wong (Ed.) Weinheim Wiley-VCH txt rdacontent n rdamedia nc rdacarrier Kohlenhydrate (DE-588)4164517-0 gnd rswk-swf Chemie (DE-588)4009816-3 gnd rswk-swf Arzneimittelforschung (DE-588)4003120-2 gnd rswk-swf Arzneimittelforschung (DE-588)4003120-2 s Kohlenhydrate (DE-588)4164517-0 s Chemie (DE-588)4009816-3 s DE-604 Wong, Chi-Huey Sonstige oth DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=012750688&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Carbohydrate-based drug discovery Kohlenhydrate (DE-588)4164517-0 gnd Chemie (DE-588)4009816-3 gnd Arzneimittelforschung (DE-588)4003120-2 gnd |
| subject_GND | (DE-588)4164517-0 (DE-588)4009816-3 (DE-588)4003120-2 |
| title | Carbohydrate-based drug discovery |
| title_auth | Carbohydrate-based drug discovery |
| title_exact_search | Carbohydrate-based drug discovery |
| title_full | Carbohydrate-based drug discovery Chi-Huey Wong (Ed.) |
| title_fullStr | Carbohydrate-based drug discovery Chi-Huey Wong (Ed.) |
| title_full_unstemmed | Carbohydrate-based drug discovery Chi-Huey Wong (Ed.) |
| title_short | Carbohydrate-based drug discovery |
| title_sort | carbohydrate based drug discovery |
| topic | Kohlenhydrate (DE-588)4164517-0 gnd Chemie (DE-588)4009816-3 gnd Arzneimittelforschung (DE-588)4003120-2 gnd |
| topic_facet | Kohlenhydrate Chemie Arzneimittelforschung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=012750688&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT wongchihuey carbohydratebaseddrugdiscovery |