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WO1998047913A3 - Inhibition of hiv-1 replication by a tat rna-binding domain peptide analog - Google Patents

Inhibition of hiv-1 replication by a tat rna-binding domain peptide analog Download PDF

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Publication number
WO1998047913A3
WO1998047913A3 PCT/US1998/007533 US9807533W WO9847913A3 WO 1998047913 A3 WO1998047913 A3 WO 1998047913A3 US 9807533 W US9807533 W US 9807533W WO 9847913 A3 WO9847913 A3 WO 9847913A3
Authority
WO
WIPO (PCT)
Prior art keywords
arg
hiv
inhibition
tat
replication
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1998/007533
Other languages
French (fr)
Other versions
WO1998047913A2 (en
Inventor
Jihong Wang
Stanley Stein
Michael J Leibowitz
Arnold B Rabson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rutgers State University of New Jersey
Rutgers Health
Original Assignee
University of Medicine and Dentistry of New Jersey
Rutgers State University of New Jersey
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 University of Medicine and Dentistry of New Jersey, Rutgers State University of New Jersey filed Critical University of Medicine and Dentistry of New Jersey
Priority to AU69727/98A priority Critical patent/AU6972798A/en
Publication of WO1998047913A2 publication Critical patent/WO1998047913A2/en
Publication of WO1998047913A3 publication Critical patent/WO1998047913A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
    • C12N2740/16322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Virology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The peptidic compounds, R-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-X-(biotin)-NH2 wherein R is the residue of a carboxylic acid and X is a cysteine or lysine residue, analogs thereof, and the biologically and pharmaceutically acceptable salts thereof, contain the 9-amino acid sequence from the basic domain of the Tat protein responsible for specific interaction with TAR RNA, or an analog thereof. The cysteine or lysine residue provides an attachment site for biotin which acts as a cellular uptake enhancer. These peptides bind a fragment of TAR RNA (ΔTAR) avidly and specifically, as measured in an electrophoretic gel shift assay. Further, they inhibit tat gene-induced expression of a stably transfected CAT (chloramphenicol acety transferase) reporter gene linked to the HIV-1 LTR in a model cell assay, but do not inhibit phorbol ester-induced expression of CAT, thereby demonstrating a Tat-dependent mechanism of inhibition. Inhibition of HIV-1 replication after acute infection of MT2 cells was demonstrated by absence of HIV-induced syncytium formation and cytotoxicity, as well as by suppression of reverse transcriptase production. These results indicate that these peptides are capable of competing with the TAR RNA-binding domain of Tat protein and thus are useful as therapeutic agents in the treatment of AIDS.
PCT/US1998/007533 1997-04-18 1998-04-16 Inhibition of hiv-1 replication by a tat rna-binding domain peptide analog Ceased WO1998047913A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU69727/98A AU6972798A (en) 1997-04-18 1998-04-16 Inhibition of hiv-1 replication by a tat rna-binding domain peptide analog

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US84444897A 1997-04-18 1997-04-18
US08/844,448 1997-04-18

Publications (2)

Publication Number Publication Date
WO1998047913A2 WO1998047913A2 (en) 1998-10-29
WO1998047913A3 true WO1998047913A3 (en) 1999-01-21

Family

ID=25292742

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/007533 Ceased WO1998047913A2 (en) 1997-04-18 1998-04-16 Inhibition of hiv-1 replication by a tat rna-binding domain peptide analog

Country Status (2)

Country Link
AU (1) AU6972798A (en)
WO (1) WO1998047913A2 (en)

Cited By (1)

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US10023615B2 (en) 2008-12-22 2018-07-17 Xigen Inflammation Ltd. Efficient transport into white blood cells

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AU8912698A (en) 1997-08-19 1999-03-08 University Of Medicine And Dentistry Of New Jersey Inhibition of hiv-1 replication using d-amino acid peptides
US6258774B1 (en) 1998-03-19 2001-07-10 University Of Medicine And Dentistry Of New Jersey Carrier for in vivo delivery of a therapeutic agent
US20030181367A1 (en) * 1999-09-27 2003-09-25 O'mahony Daniel Conjugates of membrane translocating agents and pharmaceutically active agents
CA2386231C (en) * 1999-09-27 2010-09-14 Daniel J. O'mahony Membrane translocating peptide drug delivery system
US8183339B1 (en) 1999-10-12 2012-05-22 Xigen S.A. Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US20040082509A1 (en) 1999-10-12 2004-04-29 Christophe Bonny Cell-permeable peptide inhibitors of the JNK signal transduction pathway
AU784264B2 (en) * 2000-02-07 2006-03-02 Wisconsin Alumni Research Foundation Pharmacologically active antiviral peptides and methods of their use
AU2002240312A1 (en) * 2001-02-08 2002-08-19 Pankaj Paranjp Enhanced oral and transcompartmental delivery of therapeutic or diagnostic agents using polymer conjugates
US7803749B2 (en) 2002-01-09 2010-09-28 Xigen Sa Peptide inhibitors of MKK7 kinase binding to insulin binding proteins
US7364842B2 (en) * 2003-05-19 2008-04-29 Irm, Llc Methods of identifying modulators of human retrovirus replication
US8080517B2 (en) 2005-09-12 2011-12-20 Xigen Sa Cell-permeable peptide inhibitors of the JNK signal transduction pathway
WO2007031098A1 (en) 2005-09-12 2007-03-22 Xigen S.A. Cell-permeable peptide inhibitors of the jnk signal transduction pathway
WO2009030254A1 (en) * 2007-09-04 2009-03-12 Curevac Gmbh Complexes of rna and cationic peptides for transfection and for immunostimulation
WO2009143864A1 (en) 2008-05-30 2009-12-03 Xigen S.A. Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of chronic or non-chronic inflammatory digestive diseases
WO2009143865A1 (en) 2008-05-30 2009-12-03 Xigen S.A. Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of various diseases
WO2010037408A1 (en) 2008-09-30 2010-04-08 Curevac Gmbh Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof
US20110053829A1 (en) 2009-09-03 2011-03-03 Curevac Gmbh Disulfide-linked polyethyleneglycol/peptide conjugates for the transfection of nucleic acids
IT1397569B1 (en) 2009-12-10 2013-01-16 Icgeb PEPTIDES AND THEIR DERIVATIVES THAT INHIBIT THE EXTRACELLULAR RELEASE OF HIV-1 PROTEIN TAT AND THE REPLICATION OF HIV-1.
WO2011160653A1 (en) 2010-06-21 2011-12-29 Xigen S.A. Novel jnk inhibitor molecules
CA2801523C (en) 2010-07-30 2021-08-03 Curevac Gmbh Complexation of nucleic acids with disulfide-crosslinked cationic components for transfection and immunostimulation
CA2807552A1 (en) 2010-08-06 2012-02-09 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
SMT202200321T1 (en) 2010-10-01 2022-09-14 Modernatx Inc Ribonucleic acids containing n1-methyl-pseudouracils and uses thereof
US9150618B2 (en) 2010-10-14 2015-10-06 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of chronic or non-chronic inflammatory eye diseases
WO2012116715A1 (en) 2011-03-02 2012-09-07 Curevac Gmbh Vaccination in newborns and infants
WO2012113413A1 (en) 2011-02-21 2012-08-30 Curevac Gmbh Vaccine composition comprising complexed immunostimulatory nucleic acids and antigens packaged with disulfide-linked polyethyleneglycol/peptide conjugates
WO2012116714A1 (en) 2011-03-02 2012-09-07 Curevac Gmbh Vaccination in elderly patients
WO2012135805A2 (en) 2011-03-31 2012-10-04 modeRNA Therapeutics Delivery and formulation of engineered nucleic acids
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
ES2911677T3 (en) 2011-10-03 2022-05-20 Modernatx Inc Nucleosides, nucleotides and modified nucleic acids, and their uses
US20130156849A1 (en) 2011-12-16 2013-06-20 modeRNA Therapeutics Modified nucleoside, nucleotide, and nucleic acid compositions
WO2013091670A1 (en) 2011-12-21 2013-06-27 Xigen S.A. Novel jnk inhibitor molecules for treatment of various diseases
WO2013113326A1 (en) 2012-01-31 2013-08-08 Curevac Gmbh Pharmaceutical composition comprising a polymeric carrier cargo complex and at least one protein or peptide antigen
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US9878056B2 (en) 2012-04-02 2018-01-30 Modernatx, Inc. Modified polynucleotides for the production of cosmetic proteins and peptides
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
EP2834260A4 (en) 2012-04-02 2016-08-10 Moderna Therapeutics Inc MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF MEMBRANE PROTEINS
HRP20220607T1 (en) 2012-11-26 2022-06-24 Modernatx, Inc. Terminally modified rna
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
WO2014206427A1 (en) 2013-06-26 2014-12-31 Xigen Inflammation Ltd. New use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of various diseases
AU2014301631A1 (en) 2013-06-26 2015-08-27 Xigen Inflammation Ltd. New use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
WO2015197097A1 (en) 2014-06-26 2015-12-30 Xigen Inflammation Ltd. New use for jnk inhibitor molecules for treatment of various diseases
MX369469B (en) 2013-08-21 2019-11-08 Curevac Ag Respiratory syncytial virus (rsv) vaccine.
EP3052106A4 (en) 2013-09-30 2017-07-19 ModernaTX, Inc. Polynucleotides encoding immune modulating polypeptides
EA201690675A1 (en) 2013-10-03 2016-08-31 Модерна Терапьютикс, Инк. POLYNUCLEOTES ENCODING THE RECEPTOR OF LOW DENSITY LIPOPROTEINS
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MA55321A (en) 2019-03-15 2022-01-19 Modernatx Inc RNA VACCINES AGAINST HIV
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Citations (1)

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Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
WO1992007871A1 (en) * 1990-10-24 1992-05-14 Allelix Biopharmaceuticals Inc. Peptide-based inhibitors of hiv replication

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHOUDHURY, INDRANI ET AL: "Inhibition of HIV-1 replication by a Tat RNA-binding domain peptide analog", J. ACQUIRED IMMUNE DEFIC. SYNDR. HUM. RETROVIROL. (1998), 17(2), 104-111 CODEN: JDSRET;ISSN: 1077-9450, 1998, XP002080381 *
F. HAMY ET AL.: "An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 94, no. 8, 15 April 1997 (1997-04-15), WASHINGTON US, pages 3548 - 3553, XP002080382 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10023615B2 (en) 2008-12-22 2018-07-17 Xigen Inflammation Ltd. Efficient transport into white blood cells

Also Published As

Publication number Publication date
AU6972798A (en) 1998-11-13
WO1998047913A2 (en) 1998-10-29

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