Inhibition of intracellular signal transduction by 14-3-3-binding peptides

• US 5,948,765 A
• Filed: 03/15/1996
• Issued: 09/07/1999
• Est. Priority Date: 03/15/1996
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Shaw, Andrey S., Muslin, Anthony J.
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): BORIN, MICHAEL L
• Application Number:
  US08/616,669
• Time in Patent Office: 1,271 Days
• Field of Search: 530/329-326, 514/14-17
• US Class Current: 514/21.5
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C12N 9/1205 Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases

Abstract

Compositions and methods for inhibition of the intracellular activation of a signal transducing protein comprising phosphoserine containing peptides derived from the Raf-1 protein are disclosed. The peptides bind to 14-3-3 protein and thereby prevent its association with the signal transducing peptide to block signal transduction. Also provided is an assay method for identifying a pharmacologic agent that can bind 14-3-3 protein and block signal transduction.

Claims

1. A composition comprising an isolated peptide and a 14-3-3 protein, wherein the peptide comprises an amino acid sequence as set forth in SEQ ID NO:

1 and wherein the peptide capable of binding to the 14-3-3 protein.

2. The composition of claim 1, wherein the peptide comprises SEQ ID NO:

2 or SEQ ID NO;

3.

3. The composition of claim 2, wherein the peptide comprises SEQ ID NO:

5 or 10.