Marker for neurotensin receptor

• US 5,760,188 A
• Filed: 01/25/1996
• Issued: 06/02/1998
• Est. Priority Date: 12/31/1992
• Status: Expired due to Fees

• Current Assignee: Martinex R & D Incorporated
• Original Assignee: Martin R&F Incorporated
• Inventors: Faure, Marie-Pierre, Beaudet, Alain, Gaudreau, Pierrette
• Primary Examiner(s): DAVENPORT, AVIS MICHELLE
• Application Number:
  US08/591,898
• Time in Patent Office: 859 Days
• Field of Search: 530/327, 530/328, 530/329, 530/402, 514/14, 514/15, 514/16, 514/17
• US Class Current: 530/402
• CPC Class Codes: C07K 7/083 Neurotensin
• CPC Class Codes: G01N 2333/726 G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds

Abstract

The present invention relates to compound having the formula: ##STR1## or a pharmaceutically acceptable acid salt thereof, wherein R is a polypeptide moiety comprises an amino acid sequence:

-Y-Arg-Pro-Z-Ile-Leu;

wherein Y is Arg, and

Z is Tyr or Trp;

R₁ is a fluorophore selected from the group consisting of fluorescein, rhodamine, Blue fluorescent and Texas red; and

X is oxygen or sulfur. The present invention also relates to a method for the labeling of neurotensin receptors on cell surface and a method to isolate neurotensin-receptor expressing cells.

Claims

1. A compound having a formula:

##STR5## or a pharmaceutically acceptable acid salt thereof, wherein R is a polypeptide moiety having 13 or fewer amino acid residues, and comprising an amino acid sequence;

-Y-Arg-Pro-Z-Ile-Leu;

(SEQ ID NO.;

1)

wherein Y is selected from the group consisting of Arg, Pro-Arg, A-Pro-Arg, Asn-A-Pro-Arg, Glu-Asn-A-Pro-Arg, B-Glu-Asn-A-Pro-Arg, Leu-B-Glu-Asn-A-Pro-Arg or W-Leu-B-Glu-Asn-A-Pro-Arg wherein,

A is Lys or Orn;

B is Tyr or tyr;

W is Glu or pGlu;

(SEQ ID NO;

2) and

Z is Tyr or Trp;

R₁ is a light-emitting fluorophore; and

X is oxygen or sulfur;

wherein R₁ is linked to R via an Nα

-amino group of an amino-terminal amino acid residue of Y and wherein said amino acid residue is selected from the group consisting of W, Leu, B, Glu, Asn, Pro, Lys, or Orn.

2. A compound according to claim 1, wherein said polypeptide R is neurotensin or an analog thereof.

3. A compound according to claim 1, wherein R is Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, ##STR6## is fluorescein thiocarbamyl and R is linked via its N-terminus.

5. A compound according to claim 1, wherein said fluorophore is selected from the group consisting of fluorescein, rhodamine, Blue fluorescent, and Texas red.

6. A compound according to claim 1, wherein said compound is at least 99% homogeneous.

4. A compound having the formula:

##STR7## or a pharmaceutically acceptable acid salt thereof, wherein R is a polypeptide moiety having 13 or fewer amino acid residues, and comprising the amino acid residues 8-13 of neurotensin,

R₁ is a fluorophore selected from the group consisting of fluoroscein, rhodamine, Blue fluorescent and Texas red; and

X is oxygen or sulfur.