WO2006103452A3 - Improved nitroreductase enzymes - Google Patents

Improved nitroreductase enzymes Download PDF

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Publication number
WO2006103452A3
WO2006103452A3 PCT/GB2006/001180 GB2006001180W WO2006103452A3 WO 2006103452 A3 WO2006103452 A3 WO 2006103452A3 GB 2006001180 W GB2006001180 W GB 2006001180W WO 2006103452 A3 WO2006103452 A3 WO 2006103452A3
Authority
WO
WIPO (PCT)
Prior art keywords
improved
nitroreductase
mutants
prodrug
nitroreductase enzymes
Prior art date
Application number
PCT/GB2006/001180
Other languages
French (fr)
Other versions
WO2006103452A2 (en
Inventor
Peter Francis Searle
Original Assignee
Innovata Plc
Peter Francis Searle
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 Innovata Plc, Peter Francis Searle filed Critical Innovata Plc
Publication of WO2006103452A2 publication Critical patent/WO2006103452A2/en
Publication of WO2006103452A3 publication Critical patent/WO2006103452A3/en

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Classifications

    • 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
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
    • C12N9/0036—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on NADH or NADPH (1.6)

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Novel nitroreductase mutants are disclosed, having improved converting activity for the aziridinyl prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide). The mutants have point mutations at three or more sites as compared with the E coli wild-type nitroreductase and are useful for virus- or gene-directed enzyme-prodrug therapy approaches to treating diseases such as cancer. Also provided are polynucleotides and vectors encoding the improved nitroreductases of the invention.
PCT/GB2006/001180 2005-04-01 2006-03-30 Improved nitroreductase enzymes WO2006103452A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0506642A GB0506642D0 (en) 2005-04-01 2005-04-01 Improved nitroreductase enzymes
GB0506642.8 2005-04-01

Publications (2)

Publication Number Publication Date
WO2006103452A2 WO2006103452A2 (en) 2006-10-05
WO2006103452A3 true WO2006103452A3 (en) 2006-12-14

Family

ID=34586548

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2006/001180 WO2006103452A2 (en) 2005-04-01 2006-03-30 Improved nitroreductase enzymes

Country Status (2)

Country Link
GB (1) GB0506642D0 (en)
WO (1) WO2006103452A2 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010048976A1 (en) * 2008-10-31 2010-05-06 Universita' Degli Studi Di Pavia NITROREDUCTASE NfnB FROM MYCOBACTERIUM SMEGMATIS
GB0915249D0 (en) 2009-09-02 2009-10-07 Univ Bangor Drug carrier
WO2012008860A2 (en) 2010-07-16 2012-01-19 Auckland Uniservices Limited Bacterial nitroreductase enzymes and methods relating thereto
GB201320679D0 (en) * 2013-11-22 2014-01-08 Univ Nottingham Polypeptides,polynucleotides and uses thereof
LT7046B (en) 2022-04-15 2024-02-12 Vilniaus Universitetas Hydrolases and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003018788A2 (en) * 2001-08-21 2003-03-06 Ml Laboratories Plc Improved nitroreductase enzymes

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003018788A2 (en) * 2001-08-21 2003-03-06 Ml Laboratories Plc Improved nitroreductase enzymes

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GROVE JANE I ET AL: "Generation of Escherichia coli nitroreductase mutants conferring improved cell sensitization to the prodrug CB1954.", CANCER RESEARCH, vol. 63, no. 17, 1 September 2003 (2003-09-01), pages 5532 - 5537, XP002399200, ISSN: 0008-5472 *
SEARLE PETER F ET AL: "Nitroreductase: A prodrug-activating enzyme for cancer gene therapy", CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol. 31, no. 11, November 2004 (2004-11-01), pages 811 - 816, XP002399201, ISSN: 0305-1870 *
ZENNO S ET AL: "Conversion of NfsB, a minor Escherichia coli nitroreductase, to a flavin reductase similar in biochemical properties to FRase I, the major flavin reductase in Vibrio fischeri, by a single amino acid substitution", JOURNAL OF BACTERIOLOGY, WASHINGTON, DC, US, vol. 178, no. 15, August 1996 (1996-08-01), pages 4731 - 4733, XP002227224, ISSN: 0021-9193 *

Also Published As

Publication number Publication date
GB0506642D0 (en) 2005-05-11
WO2006103452A2 (en) 2006-10-05

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