WO2000071682A3 - Crystal structure data of cysteinprotease gingipain r - Google Patents

Crystal structure data of cysteinprotease gingipain r Download PDF

Info

Publication number
WO2000071682A3
WO2000071682A3 PCT/EP2000/004561 EP0004561W WO0071682A3 WO 2000071682 A3 WO2000071682 A3 WO 2000071682A3 EP 0004561 W EP0004561 W EP 0004561W WO 0071682 A3 WO0071682 A3 WO 0071682A3
Authority
WO
WIPO (PCT)
Prior art keywords
crystal structure
gingipain
cysteinprotease
structure data
phe
Prior art date
Application number
PCT/EP2000/004561
Other languages
French (fr)
Other versions
WO2000071682A2 (en
Inventor
Andreas Eichinger
Hans-Georg Beisel
Wolfram Bode
Robert Huber
Luis Moroder
James Travis
Jan Potempa
Stefan Alefelder
Eva Pleiner
Joerg Stuerzebecher
Original Assignee
Max Planck Gesellschaft
Univ Georgia
Andreas Eichinger
Beisel Hans Georg
Wolfram Bode
Robert Huber
Luis Moroder
James Travis
Jan Potempa
Stefan Alefelder
Eva Pleiner
Joerg Stuerzebecher
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Max Planck Gesellschaft, Univ Georgia, Andreas Eichinger, Beisel Hans Georg, Wolfram Bode, Robert Huber, Luis Moroder, James Travis, Jan Potempa, Stefan Alefelder, Eva Pleiner, Joerg Stuerzebecher filed Critical Max Planck Gesellschaft
Priority to AU58088/00A priority Critical patent/AU5808800A/en
Publication of WO2000071682A2 publication Critical patent/WO2000071682A2/en
Publication of WO2000071682A3 publication Critical patent/WO2000071682A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/81—Protease inhibitors
    • G01N2333/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • G01N2333/8139—Cysteine protease (E.C. 3.4.22) inhibitors, e.g. cystatin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
    • G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
    • G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
    • G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
    • G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
    • G01N2333/96466—Cysteine endopeptidases (3.4.22)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

Abstract

The objects of the present invention are a crystal structure of gingipain R as shown in (Fig. 1) and a crystal structure of a gingipain R in complex with H-D-Phe-Phe-Arg-chloromethylketone as shown in (Fig. 4). A further object is the use of such crystal structure to obtain crystal structure data for the design and/or identification of inhibitors of gingipain R, which again form part of the present invention, as well as pharmaceutical compositions containing such inhibitors.
PCT/EP2000/004561 1999-05-20 2000-05-19 Crystal structure data of cysteinprotease gingipain r WO2000071682A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU58088/00A AU5808800A (en) 1999-05-20 2000-05-19 Crystal structure data of cysteinprotease gingipain r

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP99109944.1 1999-05-20
EP99109944 1999-05-20

Publications (2)

Publication Number Publication Date
WO2000071682A2 WO2000071682A2 (en) 2000-11-30
WO2000071682A3 true WO2000071682A3 (en) 2001-10-18

Family

ID=8238215

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/004561 WO2000071682A2 (en) 1999-05-20 2000-05-19 Crystal structure data of cysteinprotease gingipain r

Country Status (2)

Country Link
AU (1) AU5808800A (en)
WO (1) WO2000071682A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2011214908A1 (en) * 2010-02-12 2012-09-20 Sydney West Area Health Services (Swahs) Protein domains and uses therefor
US20210033531A1 (en) * 2017-09-15 2021-02-04 Stc.Unm Method and System to Mimic A Random Structural Pattern

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4973554A (en) * 1987-05-29 1990-11-27 National Research Council Of Canada Affinity process for trypsin purification and stabilization
WO1995007286A1 (en) * 1993-09-10 1995-03-16 University Of Georgia Research Foundation, Inc. Porphyromonas gingivalis arginine-specific proteinase coding sequences
WO1998049190A2 (en) * 1997-04-25 1998-11-05 Cortech, Inc. Substituted oxadiazole cysteine protease inhibitors

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4973554A (en) * 1987-05-29 1990-11-27 National Research Council Of Canada Affinity process for trypsin purification and stabilization
WO1995007286A1 (en) * 1993-09-10 1995-03-16 University Of Georgia Research Foundation, Inc. Porphyromonas gingivalis arginine-specific proteinase coding sequences
WO1998049190A2 (en) * 1997-04-25 1998-11-05 Cortech, Inc. Substituted oxadiazole cysteine protease inhibitors

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
Title
BANBULA A ET AL: "Crystallization and preliminary X-ray diffraction analysis of gingipain R2 from Porphyromonas gingivalis in complex with H-D-Phe-Phe-Arg-chloromethylketone.", PROTEIN SCIENCE, (1998 MAY) 7 (5) 1259-61., XP002120682 *
BIOORGANIC AND MEDICINAL CHEMISTRY, (1998 DEC) 6 (12) 2477-94. *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1988, STUEBER W ET AL: "SYNTHESIS OF A TRIPEPTIDE WITH A CARBOXYL-TERMINAL NITRILE MOIETY AND THE INHIBITION OF PROTEINASES", XP002164556, Database accession no. PREV198885086104 *
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1995, LALMANACH GILLES ET AL: "Conserved cystatin segments as models for designing specific substrates and inhibitors of cysteine proteinases.", XP002164557, Database accession no. PREV199698631164 *
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; SCHEIDT K A ET AL: "Structure - based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors.", XP002120877, retrieved from STN Database accession no. 1999122713 *
DATABASE XFIRE 11 July 1987 (1987-07-11), XP002164559 *
DATABASE XFIRE 11 July 1989 (1989-07-11), XP002164558 *
EICHINGER ANDREAS ET AL: "Crystal structure of gingipain R: An Arg-specific bacterial cysteine proteinase with a caspase-like fold.", EMBO (EUROPEAN MOLECULAR BIOLOGY ORGANIZATION) JOURNAL, vol. 18, no. 20, 15 October 1999 (1999-10-15), pages 5453 - 5462, XP002152750, ISSN: 0261-4189 *
INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH, vol. 31, no. 1, 1988, pages 63 - 70, ISSN: 0367-8377 *
JOURNAL OF MEDICAL CHEMISTRY, vol. 12, 1969, pages 408 *
JOURNAL OF PROTEIN CHEMISTRY, vol. 14, no. 8, 1995, pages 645 - 653, ISSN: 0277-8033 *
NISHIKATA M ET AL: "SALIVARY HISTATIN AS AN INHIBITOR OF A PROTEASE PRODUCED BY THE ORAL BACTERIUM BACTEROIDES-GINGIVALIS", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 174, no. 2, 1991, pages 625 - 630, XP002164570, ISSN: 0006-291X *
PHARMAZIE, vol. 29, 1974, pages 383 *
POTEMPA J ET AL: "Titration and mapping of the active site of cysteine proteinases from Porphyromonas gingivalis ( gingipains ) using peptidyl chloromethanes.", BIOLOGICAL CHEMISTRY, (1997 MAR-APR) 378 (3-4) 223-30., XP002120683 *
RECANATINI M ET AL: "Quantitative structure-activity relationships and molecular graphics in ligand receptor interactions: amidine inhibition of trypsin", MOLECULAR PHARMACOLOGY, vol. 29, no. 4, 1986, pages 436-446, XP000990946 *
SHINOHARA CHIKARA ET AL: "Arg-gingipain inhibition and anti-bacterial activity selective for Porphyromonas gingivalis by malabaricone C.", BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, vol. 63, no. 8, August 1999 (1999-08-01), pages 1475 - 1477, XP002164555, ISSN: 0916-8451 *
THOMPSON S K ET AL: "Structure - based design of cathepsin K inhibitors containing a benzyloxy-substituted benzoyl peptidomimetic.", JOURNAL OF MEDICINAL CHEMISTRY, (1998 OCT 8) 41 (21) 3923-7., XP002120685 *
WALSMANN P ET AL: "Synthetische Inhibitoren der Serinproteinasen", PHARMAZIE, vol. 34, no. 3, 1979, pages 194 - 195, XP000990908 *

Also Published As

Publication number Publication date
AU5808800A (en) 2000-12-12
WO2000071682A2 (en) 2000-11-30

Similar Documents

Publication Publication Date Title
HUP0104768A3 (en) 4-amino-3-oxo-azepanes as protease inhibitors and pharmaceutical compositions containing the same
ATE146360T1 (en) FREEZE-DRIED DROPS CONTAINING GONADOTROPIN
HUP0200347A2 (en) N-cyanomethylamides as protease inhibitors, pharmaceutical compositions containing them and their use
IL152315A0 (en) Soluble ctla4 mutant molecules and pharmaceutical compositions containing the same
AU2001290257A2 (en) Glucopyranosyloxybenzylbenzene derivatives and medicinal compositions containing the same
AU2001290257A1 (en) Glucopyranosyloxybenzylbenzene derivatives and medicinal compositions containing the same
NZ229832A (en) Condensed heterocyclic compounds, preparation and pharmaceutical compositions thereof
HUP0105077A3 (en) Serine protease inhibitors and pharmaceutical compositions containing them
IL159086A0 (en) 3-aryl-5-aryl- [1, 2, 4] -oxadiazole derivatives and pharmaceutical compositions containing the same
IL128942A0 (en) Inhibitors of type 5 and type 3 17beta-hydroxysteroid dehydrogenase and pharmaceutical compositions containing the same
IL145475A0 (en) Compounds that inhibit impdh enzyme and pharmaceutical compositions containing the same
IL152718A0 (en) Piperidine derivatives and pharmaceutical compositions containing the same
AU2626001A (en) Storing and retrieving the visual form of data
IL158300A0 (en) Bisarylimidazol derivatives and pharmaceutical compositions containing the same
AU7294098A (en) Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses
AU2001278821A1 (en) Novel thiocarbamic acid derivatives and the pharmaceutical compositions containing the same
IL150383A0 (en) Glyburide and pharmaceutical compositions containing the same
AU2002328494A1 (en) Drugs containing chymase inhibitor and ACE inhibitor as the active ingredients
RU2001126719A (en) Digester-substituted metalloprotease inhibitors
EP0624581A3 (en) 4-Substituted benzopyran and related compounds useful as pharmaceutical agents.
GB0108722D0 (en) Creatine and/or creatine derivatives used as cosmetic preparations containing moisturizers
HUP0200055A3 (en) 16-hydroxyestrienes and pharmaceutical compositions containing the same
AU2002333373A1 (en) Combined preparations, containing 1,4-benzothiepine-1,1-dioxide derivatives and other active substances, and the use thereof
AU2001276027A1 (en) Heteroaryl-beta-alanine derivatives as alpha 4 integrin inhibitors
DE60003943D1 (en) TRIMEGESTONE CONTAINING PHARMACEUTICAL COMPOSITIONS

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWE Wipo information: entry into national phase

Ref document number: 09979624

Country of ref document: US

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP