Design of active-site-directed irreversible enzyme inhibitors: The organic chemistry of the enzymic active-site
Saved in:
| Main Author: | |
|---|---|
| Format: | Book |
| Language: | English |
| Published: |
New York u.a.
Wiley
1967
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XIII, 325 S. graph. Darst. |
Staff View
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV001930574 | ||
| 003 | DE-604 | ||
| 005 | 20011112 | ||
| 007 | t | ||
| 008 | 890928s1967 d||| |||| 00||| eng d | ||
| 035 | |a (OCoLC)191250 | ||
| 035 | |a (DE-599)BVBBV001930574 | ||
| 040 | |a DE-604 |b ger |e rakddb | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-91G |a DE-355 |a DE-20 |a DE-83 |a DE-188 | ||
| 050 | 0 | |a QP601 | |
| 082 | 0 | |a 574.1925 |2 18 | |
| 084 | |a VK 8700 |0 (DE-625)147548:253 |2 rvk | ||
| 084 | |a CHE 828f |2 stub | ||
| 100 | 1 | |a Baker, Bernard R. |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Design of active-site-directed irreversible enzyme inhibitors |b The organic chemistry of the enzymic active-site |c Bernard Randall Baker* |
| 264 | 1 | |a New York u.a. |b Wiley |c 1967 | |
| 300 | |a XIII, 325 S. |b graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 7 | |a Enzimas |2 larpcal | |
| 650 | 4 | |a Enzymes | |
| 650 | 4 | |a Enzyme Inhibitors | |
| 650 | 4 | |a Enzyme inhibitors | |
| 650 | 0 | 7 | |a Enzyminhibitor |0 (DE-588)4152479-2 |2 gnd |9 rswk-swf |
| 689 | 0 | 0 | |a Enzyminhibitor |0 (DE-588)4152479-2 |D s |
| 689 | 0 | |5 DE-604 | |
| 856 | 4 | 2 | |m HEBIS Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=001258347&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 940 | 1 | |q TUB-nveb | |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-001258347 | ||
Record in the Search Index
| _version_ | 1804116370156158976 |
|---|---|
| adam_text | Contents
GENERAL CONSIDERATIONS 1
Enzyme Inhibitors in Chemotherapy: The 6-Mercapto-
purine story 3
Activation • Enzymes Inhibited by Thioinosinate • Cell
Membrane Permeability • Resistance • Latentiation •
Alternate Inhibitors for Feed-back Inhibition of Purine
Biosynthesis • Cell Selectivity •
Irreversible Enzyme Inhibitors 13
Esterase Inhibitors • The Azaserine Story •
The Active-Site-Directed Irreversible Enzyme Inhibitor
Concept 17
The Endo Mechanism • Bulk Tolerance in Enzyme-
Inhibitor Complexes • The Exo Mechanism •
Major Types of Enzyme Reactions 21
2 | BINDING BETWEEN GROUPS ON PROTEINS AND
SUBSTRATES OR INHIBITORS 23
General Considerations
23
Protein Groups Complexing with Substrates or Inhibitors 24
Anionic-Cationic Interactions • Hydrogen Bonds •
Charge-Transfer Complexes • Hydrophobic Bonding and
van der Waals Forces • Mixed Types •
i
ix
X
Contents
Substrate and Inhibitor Groups Complexing with Enzymes 41
General Considerations • Functional Groups •
Heterocycles •
3 | SPECIFIC MODE OF BINDING TO ENZYMES
I PROTEOLYTIC ENZYMES 48
General Considerations 48
Chymotrypsin 48
p3 Area • px Area • p2 Area • pH Area • Other
Inhibitor Types •
Trypsin 59
General Considerations • p3 Area • Area • pH Area •
p2 Area •
4 | SPECIFIC MODE OF BINDING TO ENZYMES 70
II PYRIMIDINE AREA
Thymidine Kinase 70
Ribofuranose Binding • Pyrimidine Binding •
Hydrophobic Bonding • Ribofuranose Simulation •
Thymidine Phosphorylase 79
Ribofuranose Binding • Hydrophobic Bonding •
Pyrimidine Binding •
Contrast in Thymidine Binding to Its Kinase and
Phosphorylase 93
5 | SPECIFIC MODE OF BINDING TO ENZYMES 96
HI PURINE AREA
Succinoadenylate Kinosynthetase 96
Purine Binding • Ribofuranose-5 -Phosphate Binding •
Guanine Deaminase
101
Contents xi
SUBSTRATE OR INHIBITOR? 107
Structural Change at Reaction Site 107
Chymotrypsin and Trypsin • Thymidine Kinase •
Thymidine Phosphorylase • Other Enzymes •
BULK TOLERANCE IN ENZYME-INHIBITOR 116
COMPLEXES
Chymotrypsin and Trypsin 116
Thymidine Kinase 117
Guanine Deaminase 119
Thymidine Phosphorylase 121
ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS 122
Kinetic Parameters 122
Active-Site-Directed Inactivation • Bimolecular
Inactivation • Protective Effects •
Chymotrypsin 129
Acylation of Serine-195 • Alkylation of Histidine-57 •
Alkylation of Methionine-192 • Other Inactivations •
Possible Function of Methionine in the pi Area •
Alkylation of Other Amino Acids •
Trypsin 149
Other Enzymes 152
Combining Regions of Antibodies 153
MODUS OPERANDI I LACTIC AND GLUTAMIC 156
DEHYDROGENASES
General Considerations 156
Binding Points
158
xii Contents
Bulk Tolerance
160
Active-Site-Directed Irreversible Inhibitors
165
The Bridge Principle of Specificity
172
Nucleophilic Sites • Conformational and Steric Aspects •
Inactivation via the Carbophenoxy Group • Inactivation
via the Maleamyl Group • Hindrance to the Transition
State • Bridging Phenomenon with Chymotrypsin •
Isozyme Specificity •
Enzyme Evolution 184
Experimental Design for Unexplored Enzymes 190
10 | MODUS OPERANDI II DIHYDROFOLIC REDUCTASE 192
Folate Cofactor Enzymes 192
General Considerations 196
Substrates • Types of Inhibitors • Binding
Measurements •
Hydrophobic Bonding 204
General Considerations • Mode of Aryl Binding of
1-Aryl-l ,2-Dihydro-s-Triazines • n-Alkyl Binding •
Conformational Aspects of Alkyl Binding • Aralkyl
Binding • Position of the Hydrophobic Bonding Area on
the Enzyme • Mode of Binding of Pyrimidines; pH
Profiles of Inhibitors •
Active-Site-Directed Irreversible Inhibitors 241
General Considerations • 2-Amino-4-Pyrimidinol Type •
2,4-Diaminopyrimidine Type • Other Types •
Species Differences in Dihydrofolic Reductases 252
General Differences • Hydrophobic Bonding Differences •
Relative Topography of Hydrophobic Bonding to the
Two Enzymes •
Membrane Permeability of Inhibitors
263
Contents xiii
11 | MODUS OPERANDI III OTHER FOLATE 267
COFACTOR AREA ENZYMES
5,10-Methylene-/-Tetrahydrofolate Dehydrogenase 267
Thymidylate Synthetase 269
General Considerations • Mode of Benzoyl-L-Glutamate
Binding • Mode of Pyrimidine Binding • Mode of
Anilino Binding • Bridge Variation Between Pyrimidyl
and Phenyl Moieties • Bulk Tolerance • Hydrophobic
Bonding •
12 | MODUS OPERANDI IV ADENOSINE DEAMINASE 285
General Considerations 285
Ribofuranose Binding 286
Purine Binding 289
Hydrophobic Bonding 291
Hydroxyalkyl Binding 293
Active-Site-Directed Irreversible Inhibition 295
13 | ENZYME-SPECIFIC COLUMNS 301
Notation 309
Author Index 311
Subject Index
|
| any_adam_object | 1 |
| author | Baker, Bernard R. |
| author_facet | Baker, Bernard R. |
| author_role | aut |
| author_sort | Baker, Bernard R. |
| author_variant | b r b br brb |
| building | Verbundindex |
| bvnumber | BV001930574 |
| callnumber-first | Q - Science |
| callnumber-label | QP601 |
| callnumber-raw | QP601 |
| callnumber-search | QP601 |
| callnumber-sort | QP 3601 |
| callnumber-subject | QP - Physiology |
| classification_rvk | VK 8700 |
| classification_tum | CHE 828f |
| ctrlnum | (OCoLC)191250 (DE-599)BVBBV001930574 |
| dewey-full | 574.1925 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 574 - [Unassigned] |
| dewey-raw | 574.1925 |
| dewey-search | 574.1925 |
| dewey-sort | 3574.1925 |
| 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>01445nam a2200397 c 4500</leader><controlfield tag="001">BV001930574</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20011112 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">890928s1967 d||| |||| 00||| eng d</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)191250</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV001930574</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="049" ind1=" " ind2=" "><subfield code="a">DE-91G</subfield><subfield code="a">DE-355</subfield><subfield code="a">DE-20</subfield><subfield code="a">DE-83</subfield><subfield code="a">DE-188</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QP601</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">574.1925</subfield><subfield code="2">18</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">VK 8700</subfield><subfield code="0">(DE-625)147548:253</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">CHE 828f</subfield><subfield code="2">stub</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Baker, Bernard R.</subfield><subfield code="e">Verfasser</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Design of active-site-directed irreversible enzyme inhibitors</subfield><subfield code="b">The organic chemistry of the enzymic active-site</subfield><subfield code="c">Bernard Randall Baker*</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">New York u.a.</subfield><subfield code="b">Wiley</subfield><subfield code="c">1967</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XIII, 325 S.</subfield><subfield code="b">graph. Darst.</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=" " ind2="7"><subfield code="a">Enzimas</subfield><subfield code="2">larpcal</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Enzymes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Enzyme Inhibitors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Enzyme inhibitors</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Enzyminhibitor</subfield><subfield code="0">(DE-588)4152479-2</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Enzyminhibitor</subfield><subfield code="0">(DE-588)4152479-2</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="5">DE-604</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HEBIS 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=001258347&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="940" ind1="1" ind2=" "><subfield code="q">TUB-nveb</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-001258347</subfield></datafield></record></collection> |
| id | DE-604.BV001930574 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T15:37:25Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-001258347 |
| oclc_num | 191250 |
| open_access_boolean | |
| owner | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-20 DE-83 DE-188 |
| owner_facet | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-20 DE-83 DE-188 |
| physical | XIII, 325 S. graph. Darst. |
| psigel | TUB-nveb |
| publishDate | 1967 |
| publishDateSearch | 1967 |
| publishDateSort | 1967 |
| publisher | Wiley |
| record_format | marc |
| spelling | Baker, Bernard R. Verfasser aut Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site Bernard Randall Baker* New York u.a. Wiley 1967 XIII, 325 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Enzimas larpcal Enzymes Enzyme Inhibitors Enzyme inhibitors Enzyminhibitor (DE-588)4152479-2 gnd rswk-swf Enzyminhibitor (DE-588)4152479-2 s DE-604 HEBIS Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=001258347&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Baker, Bernard R. Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site Enzimas larpcal Enzymes Enzyme Inhibitors Enzyme inhibitors Enzyminhibitor (DE-588)4152479-2 gnd |
| subject_GND | (DE-588)4152479-2 |
| title | Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site |
| title_auth | Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site |
| title_exact_search | Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site |
| title_full | Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site Bernard Randall Baker* |
| title_fullStr | Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site Bernard Randall Baker* |
| title_full_unstemmed | Design of active-site-directed irreversible enzyme inhibitors The organic chemistry of the enzymic active-site Bernard Randall Baker* |
| title_short | Design of active-site-directed irreversible enzyme inhibitors |
| title_sort | design of active site directed irreversible enzyme inhibitors the organic chemistry of the enzymic active site |
| title_sub | The organic chemistry of the enzymic active-site |
| topic | Enzimas larpcal Enzymes Enzyme Inhibitors Enzyme inhibitors Enzyminhibitor (DE-588)4152479-2 gnd |
| topic_facet | Enzimas Enzymes Enzyme Inhibitors Enzyme inhibitors Enzyminhibitor |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=001258347&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT bakerbernardr designofactivesitedirectedirreversibleenzymeinhibitorstheorganicchemistryoftheenzymicactivesite |