Glucose transporter vesicle aminopeptidase

• US 5,972,680 A
• Filed: 09/19/1995
• Issued: 10/26/1999
• Est. Priority Date: 09/20/1994
• Status: Expired due to Fees

• Current Assignee: Bayer Corporation (Bayer AG)
• Original Assignee: Bayer Corporation (Bayer AG)
• Inventors: Clairmont, Kevin B., Letsinger, John T., Knowles, William J., Hart, John T., Haigh, Wallace, Guralski, Donna
• Primary Examiner(s): Achutamurthy, Ponnathapura
• Assistant Examiner(s): Nashed, Nashaat T.
• Application Number:
  US08/530,792
• Time in Patent Office: 1,498 Days
• Field of Search: 435/219, 435/212, 435/226, 435/325, 435/320.1, 435/252.3, 435/252.33, 536/23.1, 536/23.2, 536/23.5
• US Class Current: 435/219
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 9/48 acting on peptide bonds (3.4)
• CPC Class Codes: C12Q 1/37 involving peptidase or proteinase
• CPC Class Codes: G01N 2333/8103 Exopeptidase (E.C. 3.4.11-19) inhibitors
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes

Abstract

An aminopeptidase which is a component of GLUT4-containing vesicles in the natural state, and which cleaves insulin. The claimed protein has an apparent molecular weight of approximately 110 kD in its deglycosylated form and a predicted molecular weight of 117,239 Daltons. It includes the amino acid sequences Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala (SEQ ID NO: 1) and Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Met (SEQ ID NO: 2, and reacts with antibodies produced against the peptide identified as (SEQ ID NO: 1). It is encoded by the cDNA of FIG. 20 (SEQ. ID NOs. 15 and 16) and is essentially the protein sequence therein described. Modulators of the activity of the aminopeptidase and a method for treating syndromes of insulin resistance, including diabetes, by administration of such a modulator are also claimed.

Claims

1. A purified nucleic acid sequence which is Seq ID No. 15 or Seq ID No. 16.

2. The purified nucleic acid of claim 1, said nucleic acid being under the transcriptional control of a heterologous promoter.

3. A vector comprising a nucleic acid of claim 1.

4. A transformed cell comprising a vector of claim 1.

5. A cell of claim 4 which is a mammalian cell.

6. A method comprising culturing a transformed cell which comprises a vector comprising nucleic acid Seq ID No. 15 or Seq ID No. 16 in an appropriate medium, permitting the protein encoded by the nucleic acid to be expressed in the culture, and recovering the protein from the culture.