DK1797115T3 - Bakterielt atp-synthasebindingsdomæne. - Google Patents

Bakterielt atp-synthasebindingsdomæne. Download PDF

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DK1797115T3
DK1797115T3 DK05794520.6T DK05794520T DK1797115T3 DK 1797115 T3 DK1797115 T3 DK 1797115T3 DK 05794520 T DK05794520 T DK 05794520T DK 1797115 T3 DK1797115 T3 DK 1797115T3
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atpe
amino acids
protein
atpe protein
dimensional structure
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DK05794520.6T
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Jonge Marc René De
K J L M Janssenpharmaceutica N V Andries
Hinrich W H Janssen Pharmaceutica N V Göhlmann
J -M E F M Janssen Pharmaceutica N V Neefs
Peter K M Janssen Pharmaceutica N V Verhasselt
Johann Janssen Pharmaceutica N V Winkler
Lucien Maria Henricus Molmo Services Bvba Koymans
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Janssen Pharmaceutica Nv
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    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
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    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/35Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Mycobacteriaceae (F)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Claims (14)

1. Isoleret mutant atpE-protein, der omfatter en polypeptidsekvens valgt blandt SEQ ID NO: 01, der omfatter mindst én punktmutation placeret i en hvilken som helst af ATPase-bindingsstederne, der er placeret mellem aminosyrerne 14 til 34 eller mellem aminosyrerne 54 til 69, og SEQ ID NO: 03, der omfatter mindst én punktmutation placeret i en hvilken som helst af aminosyrerne 20 til 40 eller aminosyrerne 60 til 75, hvor proteinet inducerer resistens over for den antimikrobielle forbindelse DARQJ i figur 1.
2. Isoleret mutant atpE-protein ifølge krav 1, der omfatter en polypeptidsekvens valgt fra gruppen, der består af SEQ ID NO: 01, der omfatter mindst én punktmutation placeret i aminosyre 28 eller i aminosyre 63.
3. Isoleret mutant atpE-protein ifølge krav 1 eller 2, der er valgt blandt Mtb_R som vist i SEQ ID NO: 2, Msm_R0 9 som vist i SEQ ID NO: 4, Msm_R10 som vist i SEQ ID NO: 5.
4. Anvendelse af et polypeptid ifølge et hvilket som helst af kravene 1 til 3 i en fremgangsmåde til identificering af forbindelser, der interagerer med Fo-delen af en ATPase, og deres potentiale som antimikrobielle forbindelser.
5. Fremgangsmåde til evaluering af potentialet hos en testforbindelse for at interagere med et atpE-protein, hvilken fremgangsmåde omfatter; - molekylære modelleringsteknikker til frembringelse af den tredimensionelle struktur af et bindingssted ifølge et hvilket som helst af kravene 1 til 3; - anvendelse af et computerbaseret middel til udførelse af en tilpasningsoperation mellem testforbindelsen og den tredimensionelle struktur af bindingsstedet; og analyse af resultaterne af tilpasningsoperationen til kvantificering af forbindelsen mellem testforbindelsen og den tredimensionelle struktur af bindingsstedet.
6. Fremgangsmåde ifølge krav 5, hvor den tredimensionelle struktur frembringes ved hjælp af mindst aminosyrerne Ala24, Gly27, Phe53, Val57, Gly58, Glu61, Tyr64 og Phe65 i én C-subunit og aminosyrerne Ser182, Leu183, Leu185 og Arg186 i én A-subunit ved anvendelse af atomkoordinaterne ifølge en hvilken som helst af tabellerne 3, 4 eller 5 eller homologe strukturkoordinater, der omfatter en kvadratrod af middelkvadratafvigelsen for ikke-hydrogenatomer på mindre end ca. 1,5 Å.
7. Fremgangsmåde ifølge krav 5, hvor den tredimensionelle struktur frembringes ved anvendelse af atomkoordinaterne for aminosyrerne Ala21, Gly25 i A-kæden ifølge en hvilken som helst af tabellerne 3, 4 eller 5; aminosyrerne Ala24, Gly27, Phe53, Phe54, Val57, Gly58, Glu61, Tyr64, Phe65 i K-kæden ifølge en hvilken som helst af tabellerne 3, 4 eller 5; aminosyrerne Met17, Gly19 Gly20, Ala21, Ile22, Gly23, Ala24, Gly25, Ile26, Gly27, Asp28, Gly29, Ala31, Phe53, Thr56, Val57, Gly58, Leu59, Val60, Glu61, Ala62, Ala63/Pro63, Tyr64, Phe65 i L-kæden ifølge en hvilken som helst af tabellerne 3, 4 eller 5; og aminosyrerne Ser182, Leu183, Leu185 og Arg186 i M-kæden ifølge en hvilken som helst af tabellerne 3, 4 eller 5.
8. Isoleret nukleinsyresekvens, der koder for et isoleret mutant atpE-protein ifølge et hvilket som helst af kravene 1 til 3.
9. Vektor, der omfatter nukleinsyresekvensen ifølge krav 8.
10. Værtscelle, der bærer vektoren ifølge krav 9.
11. Fremgangsmåde til identificering af en antimikrobiel forbindelse, hvilken fremgangsmåde omfatter a) etablering af kontakt mellem celler, der udtrykker et atpE-protein, og en testforbindelse under fysiologiske betingelser og b) bestemmelse af, om testforbindelsen interagerer med atpE-proteinet, hvor atpE-proteinet er et mutant atpE-protein ifølge et hvilket som helst af kravene 1 til 3.
12. Fremgangsmåde til evaluering af potentialet hos en testforbindelse for at interagere med et mutant atpE-protein ifølge et hvilket som helst af kravene 1 til 3, hvilken fremgangsmåde omfatter; a) anvendelse af molekylære modelleringsteknikker til formulering af en tredimensionel struktur af det mutante atpE-protein ifølge et hvilket som helst af kravene 1 til 3; b) anvendelse af et computerbaseret middel til udførelse af en tilpasningsoperation mellem testforbindelsen og den tredimensionelle struktur af det mutante atpE-protein ifølge kravene 1 til 3; og c) analyse af resultaterne af tilpasningsoperationen til kvantificering af forbindelsen mellem testforbindelsen og den tredimensionelle struktur af det mutante atpE-protein ifølge kravene 1 til 3.
13. Fremgangsmåde ifølge krav 12, hvor den tredimensionelle struktur af atpE-proteinet frembringes ved anvendelse af atomkoordinaterne for Ile28, Glu51 og Ile63 fra E. coli (proteindatabase 1Q01) +/- en kvadratrod af middelkvadratafvigelsen for rygradsatomerne i aminosyrerne på højst 10 Å.
14. Fremgangsmåde ifølge krav 12, hvor den tredimensionelle struktur af atpE-proteinet frembringes ved anvendelse af atomkoordinaterne ifølge tabellerne 6 eller 7 +/- en kvadratrod af middelkvadratafvigelsen for rygradsatomerne i aminosyrerne på højst 1,5 Å.
DK05794520.6T 2004-09-28 2005-09-28 Bakterielt atp-synthasebindingsdomæne. DK1797115T3 (da)

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EP04104720 2004-09-28
US62050004P 2004-10-20 2004-10-20
PCT/EP2005/054893 WO2006035051A1 (en) 2004-09-28 2005-09-28 A bacterial atp synthase binding domain

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GB2440736A (en) * 2006-08-10 2008-02-13 Medical Res Council Crystals of mutant p53 polypeptidtes
JO3271B1 (ar) 2006-12-06 2018-09-16 Janssen Pharmaceutica Nv مشتقات الكوينولين المضادة للجراثيم
JO2970B1 (en) 2006-12-06 2016-03-15 جانسين فارماسوتيكا ان. في Quinoline antibacterial derivatives
JO2685B1 (en) 2006-12-06 2013-03-03 جانسين فارماسوتيكا ان في Quinoline antibacterial derivatives
EA038350B1 (ru) 2012-04-27 2021-08-12 Янссен Фармацевтика Нв Антибактериальные хинолиновые производные
ES2576491T3 (es) 2012-04-27 2016-07-07 Janssen Pharmaceutica, N.V. Derivados de quinolina antibacterianos
US8454434B1 (en) * 2012-06-15 2013-06-04 Igt Gaming system and method for providing an offer and acceptance game with progressive awards associated with a quantity of progressive tokens
JP5580383B2 (ja) 2012-10-05 2014-08-27 株式会社 資生堂 美容機器及び通電方法及び記録媒体
KR101522087B1 (ko) * 2013-06-19 2015-05-28 삼성에스디에스 주식회사 미스매치를 고려한 염기 서열 정렬 시스템 및 방법
CN110373399B (zh) * 2019-07-09 2021-05-28 湖南省植物保护研究所 一种沼泽红假单胞菌Atps2蛋白及其制备方法和应用

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WO1993009103A1 (en) 1991-11-01 1993-05-13 The Upjohn Company Substituted aryl- and heteroarylphenyloxazolidinones useful as antibacterial agents
US6583266B1 (en) * 1993-08-19 2003-06-24 Genome Therapeutics Corporation Nucleic acid and amino acid sequences relating to mycobacterium tuberculosis and leprae for diagnostics and therapeutics
JP2004509069A (ja) * 2000-05-19 2004-03-25 ジェネティックス・インスチチュート・リミテッド・ライアビリティ・カンパニー P−セレクチン、p−およびe−セレクチン複合体の結晶構造、ならびにそれらの用途
US20040101907A1 (en) * 2000-09-19 2004-05-27 Bussiere Dirksen E. Characterization of the gsk-3beta protein and methods of use thereof
AU2002306849A1 (en) * 2001-03-21 2002-10-08 Elitra Pharmaceuticals, Inc. Identification of essential genes in microorganisms
EP1443937B1 (en) * 2001-11-13 2008-06-18 Ortho-McNeil Pharmaceuticals, Inc. Substituted 1,4-benzodiazepines and uses thereof for the treatment of cancer
PL222801B1 (pl) 2002-07-25 2016-09-30 Janssen Pharmaceutica Nv Pochodne chinoliny, ich zastosowanie, sposób ich wytwarzania oraz kompozycja farmaceutyczna zawierająca je
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HK1114619A1 (zh) 2008-11-07
AU2012216368B2 (en) 2017-04-13
KR20070073823A (ko) 2007-07-10
JP2008515395A (ja) 2008-05-15
JP2012210210A (ja) 2012-11-01
CN101065397A (zh) 2007-10-31
RS56357B1 (sr) 2017-12-29
CA2579971A1 (en) 2006-04-06
HRP20171388T1 (hr) 2017-11-03
ZA200702540B (en) 2008-08-27
RU2007116144A (ru) 2008-11-10
NO342699B1 (no) 2018-07-09
IL182185A0 (en) 2007-07-24
EP1797115A1 (en) 2007-06-20
AU2012216368A1 (en) 2012-09-13
JP5837852B2 (ja) 2015-12-24
US20090298874A1 (en) 2009-12-03
HUE033609T2 (en) 2017-12-28
EP1797115B1 (en) 2017-06-21
US8378085B2 (en) 2013-02-19
SI1797115T1 (sl) 2017-10-30
AU2005288848A1 (en) 2006-04-06
RU2418001C2 (ru) 2011-05-10
ME02935B (me) 2018-04-20
US20120219964A1 (en) 2012-08-30
CN101065397B (zh) 2015-10-21
PL1797115T3 (pl) 2017-12-29
NO20072237L (no) 2007-06-25
IL182185A (en) 2017-12-31
KR101539021B1 (ko) 2015-07-23
PT1797115T (pt) 2017-08-29
US8088891B2 (en) 2012-01-03
NZ553693A (en) 2012-05-25
WO2006035051A1 (en) 2006-04-06
LT1797115T (lt) 2017-10-10
CY1119568T1 (el) 2018-03-07
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