Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1995-03-29
1998-09-15
Allen, Marianne P.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
536 235, 536 243, 536 2431, 536 2433, 435 6, 435 691, 4353201, 435325, 530350, C12N 1500, C07K 14705
Patent
active
058076913
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new polypeptides and to the genetic material permitting their expression. More especially, it relates to new polypeptides having serotonin receptor activity.
Serotonin is a neuromodulator capable of inducing and modulating a wide variety of behavioral functions such as sleep, appetite, locomotion, sexual activity and vascular contraction. It is accepted that serotonin activity is mediated by interaction of the compound with receptors, designated serotonin receptors or 5-HT (for 5-hydroxytryptamine) receptors. Molecular biology studies as well as pharmacological studies have revealed the existence of a large number of subtypes of 5-HT receptors. The 5-HT receptors which have been described to date belong either to the family of receptors associated with ion channels (5-HT3 receptors), or to the family of receptors which interact with G proteins and which possess seven transmembrane domains. Moreover, analysis of the amino acid sequences has shown that the 5-HT receptors which interact with G proteins may be subdivided into two distinct groups: 5HT1 receptors, comprising the mammalian subtypes 5HT1A, 5HT1B and 5HT1D, as well as three drosophila 5HT receptors; and 5HT2 receptors comprising the subtypes 5HT2 and 5HT1C.
These receptors are doubtless not the only 5HT receptors which exist, inasmuch as pharmacological studies have revealed other subtypes, such as 5HT4 receptors as well as some receptors related to the subtype 5HT1 ("5HT1 -like" receptors). Furthermore, additional molecular biology studies have also revealed heterogeneities within the subtypes 5HT1 B/1 D.
The present invention is the outcome of the demonstration of new polypeptides having serotonin receptor activity. While belonging to the family of receptors which interact with G proteins, these new polypeptides differ from the serotonin receptors already described (5HT1, 5HT2, 5HT3 and 5HT4) from both a structural standpoint and a pharmacological standpoint. More especially, the invention is the outcome of the isolation and characterization of these new polypeptides, designated 5HT5a, and also of the genetic material permitting their expression or identification.
A first subject of the invention hence lies in polypeptides comprising all or part of the sequence SEQ ID No. 1 or of a derivative of the latter.
For the purposes of the present invention, the term derivative denotes any molecule obtained by modification, of a genetic and/or chemical nature, of the peptide sequence SEQ ID No. 1. Modification of a genetic and/or chemical nature may be understood to mean any mutation, substitution, deletion, addition and/or modification of one or more residues. Such derivatives may be generated for different purposes, such as, in particular, that of increasing the affinity of the peptide for its ligand(s), that of improving its levels of production, that of increasing its resistance to proteases, that of increasing and/or modifying its activity or that of endowing it with new pharmacokinetic and/or biological properties. Among derivatives resulting from an addition, chimeric polypeptides containing an additional heterologous portion attached at one end may, for example, be mentioned. The term derivative also comprises polypeptides homologous with the polypeptide SEQ ID No. 1, originating from other cell sources, and in particular from cells of human origin or of other organisms and possessing an activity of the same type. Such homologous polypeptides may be obtained by hybridization experiments, as described in the examples. In particular, the invention also relates to the peptides of sequence SEQ ID No. 8 corresponding to the human receptor.
Preferably, the polypeptides of the invention are polypeptides possessing the capacity to bind serotonin. Still more preferably, they are polypeptides having serotonin receptor activity. Still according to a preferred embodiment, the polypeptides of the invention are capable of being recognized by antibodies which recognize the complete peptide sequence SEQ ID No. 1.
A particular embo
REFERENCES:
patent: 5155218 (1992-10-01), Weinshank et al.
patent: 5389527 (1995-02-01), Beavo et al.
Proc. Natl. Acad. Sci. USA 89(12):5517-21, 1992, McAllister Charlesworth Snodin, Beer Noble et al., Molecular Cloning of a Serotonin Receptor From Human Brain (5HT1E): A Fifth 5HT1-Like Subtype.
Amlaiky Nourdine
Boschert Ursula
Hen Rene
Plassat Jean-Luc
Allen Marianne P.
Institut National De La Sante et Da La Recherche Medicale
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