WO2002068933A3 - Conception de petites molecules efficaces contre des mutants resistants aux medicaments au moyen d'evolution dirigee - Google Patents

Conception de petites molecules efficaces contre des mutants resistants aux medicaments au moyen d'evolution dirigee Download PDF

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Publication number
WO2002068933A3
WO2002068933A3 PCT/US2002/006238 US0206238W WO02068933A3 WO 2002068933 A3 WO2002068933 A3 WO 2002068933A3 US 0206238 W US0206238 W US 0206238W WO 02068933 A3 WO02068933 A3 WO 02068933A3
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WO
WIPO (PCT)
Prior art keywords
drug
sep
target protein
variant
protein
Prior art date
Application number
PCT/US2002/006238
Other languages
English (en)
Other versions
WO2002068933A2 (fr
Inventor
Raymond C Stevens
Maria C Orencia
Jun S Yoon
Michael A Hanson
Original Assignee
Scripps Research Inst
Raymond C Stevens
Maria C Orencia
Jun S Yoon
Michael A Hanson
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 Scripps Research Inst, Raymond C Stevens, Maria C Orencia, Jun S Yoon, Michael A Hanson filed Critical Scripps Research Inst
Priority to AU2002254077A priority Critical patent/AU2002254077A1/en
Publication of WO2002068933A2 publication Critical patent/WO2002068933A2/fr
Publication of WO2002068933A3 publication Critical patent/WO2002068933A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/047—Simultaneous synthesis of different peptide species; Peptide libraries
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B15/00—ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
    • G16B15/30—Drug targeting using structural data; Docking or binding prediction
    • 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)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C12N9/86—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in cyclic amides, e.g. penicillinase (3.5.2)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/02—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amides (3.5.2)
    • C12Y305/02006—Beta-lactamase (3.5.2.6)
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B15/00—ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
    • G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
    • G16C20/50—Molecular design, e.g. of drugs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Physics & Mathematics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Theoretical Computer Science (AREA)
  • Biophysics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medical Informatics (AREA)
  • Evolutionary Biology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Computing Systems (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne des procédés permettant de concevoir des nouveaux médicaments utiles contre des cellules bactériennes, des virus, des cellules mammifères et analogues résistants aux médicaments. Le procédé consiste à identifier une protéine cible du médicament, à sélectionner des variants résistants aux médicaments présentant une protéine cible modifiée (protéine de variant) par évolution dirigée, à déterminer la structure tridimensionnelle de la cible et des protéines de variant et à concevoir un nouveau médicament efficace contre au moins un variant résistant aux médicaments. Les procédés selon l'invention peuvent également être utilisés pour prévoir des mutations futures menant à une résistance aux médicaments et le type de médicaments efficace pour combattre une telle résistance.
PCT/US2002/006238 2001-02-28 2002-02-27 Conception de petites molecules efficaces contre des mutants resistants aux medicaments au moyen d'evolution dirigee WO2002068933A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002254077A AU2002254077A1 (en) 2001-02-28 2002-02-27 Small molecule design against drug resistant mutants using directed evolution

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US27224801P 2001-02-28 2001-02-28
US60/272,248 2001-02-28

Publications (2)

Publication Number Publication Date
WO2002068933A2 WO2002068933A2 (fr) 2002-09-06
WO2002068933A3 true WO2002068933A3 (fr) 2002-11-21

Family

ID=23039020

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/006238 WO2002068933A2 (fr) 2001-02-28 2002-02-27 Conception de petites molecules efficaces contre des mutants resistants aux medicaments au moyen d'evolution dirigee

Country Status (2)

Country Link
AU (1) AU2002254077A1 (fr)
WO (1) WO2002068933A2 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030027315A1 (en) * 2001-09-24 2003-02-06 Ada Yonath Methods of growing crystals of free and antibiotic complexed large ribosomal subunits, and methods of rationally designing or identifying antibiotics using structure coordinate data derived from such crystals
ATE385253T1 (de) * 2002-10-29 2008-02-15 Boehringer Ingelheim Int Nhibitor-resistente hcv ns3 protease
US8187874B2 (en) 2003-10-27 2012-05-29 Vertex Pharmaceuticals Incorporated Drug discovery method
WO2005042570A1 (fr) 2003-10-27 2005-05-12 Vertex Pharmaceuticals Incorporated Mutants resistant a la protease hcv ns3-ns4a
US20100035945A1 (en) * 2004-12-06 2010-02-11 Xiaodong Cheng Small molecule inhibitors of bacterial dam dna methyltransferases
US7705138B2 (en) 2005-11-11 2010-04-27 Vertex Pharmaceuticals Incorporated Hepatitis C virus variants
WO2015002860A1 (fr) * 2013-07-02 2015-01-08 Epigenetx, Llc Modélisation basée sur la structure et prédiction de sélectivité cible
CN105593865A (zh) * 2013-07-17 2016-05-18 西门子股份公司 用于确定对抗生素药物的细菌抗性的方法和系统
CN112269795B (zh) * 2020-10-31 2022-05-13 武汉中海庭数据技术有限公司 一种nds数据快速测试和验证的方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4461619A (en) * 1981-12-29 1984-07-24 Medical College Of Georgia Research Inst. Method of predicting biological activity of compounds by nucleic acid models
US5837500A (en) * 1988-09-02 1998-11-17 Dyax, Corp. Directed evolution of novel binding proteins
US6174678B1 (en) * 1998-10-23 2001-01-16 Small Molecule Therapeutics, Inc. Methods and compositions for modulation of bacterial topoisomerase enzymes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4461619A (en) * 1981-12-29 1984-07-24 Medical College Of Georgia Research Inst. Method of predicting biological activity of compounds by nucleic acid models
US5837500A (en) * 1988-09-02 1998-11-17 Dyax, Corp. Directed evolution of novel binding proteins
US6174678B1 (en) * 1998-10-23 2001-01-16 Small Molecule Therapeutics, Inc. Methods and compositions for modulation of bacterial topoisomerase enzymes

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GREER ET AL.: "Application of the three-dimensional structures of protein target molecules in structure-based drug design", JOURNAL OF MEDICINAL CHEMISTRY, vol. 37, no. 8, 15 April 1994 (1994-04-15), pages 1035 - 1054, XP002116744 *
KNEGTEL ET AL.: "Molecular docking to ensembles of protein structures", JOURNAL OF MOLECULAR BIOLOGY, vol. 266, no. 2, 21 February 1997 (1997-02-21), pages 424 - 440, XP002941898 *

Also Published As

Publication number Publication date
WO2002068933A2 (fr) 2002-09-06
AU2002254077A1 (en) 2002-09-12

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