Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-02-11
2000-11-14
Mertz, Prema
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
536 235, 530350, 435 711, 435 712, 435 691, 435 321, 435325, 4352523, 43525411, 435471, C12N 1512, C07K 14705, G01N 3353
Patent
active
061468355
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new polypeptides and the genetic material permitting their expression. More particularly, it relates to new polypeptides having a human kappa opioid receptor activity.
Opioid receptors are membranous receptors of the nervous system which modulate the analgesic and psychotropic properties of alkaloid drugs of the morphine type (Brownstein, 1993, Proc. Natl. Acad. Sci. USA, Vol. 90, 5391). Pharmacological studies have demonstrated the existence of three subtypes of receptors, called mu, delta and kappa, which differ by their capacity to bind to different opioid ligands (Goldstein et al., 1989, Mol. Pharmacol., Vol. 36, 265-272) and by their distribution in the organism (Mansour et al., 1987, J. Neurosci., Vol. 7, 2445). Recently, three opioid receptors have been cloned in rodents. The pharmacological profile of these three cloned receptors, expressed transitorily in Cos cells, indicate that there is a delta receptor, a mu receptor and a kappa receptor. Analysis of their primary structure confirms that they are part of the family of receptors coupled to the G proteins, which have a putative topology with seven transmembranal domains (Bockaert, 1991, Curr. Op. Neurobiol., Vol. 1, 32).
The present invention comprises the elucidation, isolation and molecular characterization of the human kappa opioid receptor. It comprises particularly the isolation and sequencing of the gene coding for this receptor, in the construction of recombinant strains permitting the expression of functional receptors, and in the elaboration of tests permitting the isolation of compounds active on these receptors and having desirable therapeutic properties. The DNA sequences of the invention also permit the provision of probes capable of detecting in biological specimens any irregularity in the expression of a kappa opioid receptor (non-expression, mutation, polymorphism, etc.). These probes are also usable for cloning by hybridization of any other cDNA coding for an opioid receptor, from tissues of diverse origins and particularly of human origin.
A first object of the invention therefore resides in a nucleotide sequence coding for a polypeptide having a human kappa opioid receptor activity.
More preferably, the nucleotide sequence according to the invention is selected from: strand, polypeptide having human kappa opioid receptor activity, and, genetic code.
The different nucleotide sequences of the invention can be of artificial origin or not. They can be genome sequences, cDNA sequences, RNA sequences, hybrid sequences or synthetic or semi-synthetic sequences. These sequences can be obtained for example by screening DNA banks (cDNA bank, DNA genome bank) by means of probes developed on the basis of the sequence SEQ ID No. 1. Such banks can be prepared from cells of different origins by conventional bimolecular techniques known to those in the art. The nucleotide sequences of the invention can also be prepared by chemical synthesis, particularly according to the phosphoramidites method, or again by mixed methods including chemical or enzymatic modification of sequences obtained by scanning banks.
The nucleotide sequences of the invention can be used for the production of kappa opioid polypeptides. The term kappa opioid polypeptide designates any polypeptide having a kappa opioid receptor activity, and any fragment or derivative of such a polypeptide. For the production of kappa opioid polypeptides, the coding portion for said polypeptide is generally placed below the signal control permitting its expression in a cellular host. The choice of these signals (promoters, terminators, etc.) can vary as a function of the cellular host utilized. To this end, the nucleotide sequences of the invention can be a part of a vector, which can have autonomous or integrated replication. More particularly, the autonomous replication vectors can be prepared by using autonomous replication sequences in the selected host. Acting on the integrative vectors, these latter can be prepared for example by using sequences homologo
REFERENCES:
Miyuki Nishi et al., "cDNA Cloning and Pharmacological Characterization of an Opioid Receptor with High Affinities for .kappa.-subtype-selective Ligands", pp. 77-80, vol. 330, No. 1, Sep. 1993, Federation of European Biochemical Societies.
Masabumi Minami et al., "Cloning and Expression of a cDNA for the Rat .kappa.-Opioid Receptor", pp. 291-294, vol. 329, No. 3, Aug. 1993, Federation of European Biochemical Societies.
Kazuki Yasuda et al., "Cloning and Functional Comparison of .kappa. and .delta. Opioid Receptors from Mouse Brain", pp. 6736-6740, vol. 90, Jul. 1993, Proc. Natl. Acad. Sci., USA, Neurobiology.
Erik Mannson, et al., "Isolation of a Human .kappa. Opioid Receptor cDNA From Placenta", pp. 1431-1437, Biochemical and Biophysical Research Communications, vol. 202, No. 3, 1994.
Guo-xi Xie et al., "Primary Structure and Functional Expression of a Guinea Pig .kappa. Opioid (dynorphin) Receptor", pp. 3779-3784, Proc. Natl. Acad. Sci. USA, vol. 91, Apr. 1994 Pharmacology.
Fan Meng et al., "Cloning and Pharmacological Characterization of a Rat .kappa. Opioid Receptor", pp. 9954-9958, Proc. Natl. Acad. Sci. USA, vol. 90, Nov. 1993 Pharmacology.
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Kieffer Brigitte
Simonin Frederic
Mertz Prema
Universite Louis Pasteur
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