Kinase anchor protein muteins, peptides thereof and related documents

• US 7,432,342 B2
• Filed: 05/01/2003
• Issued: 10/07/2008
• Est. Priority Date: 05/03/2002
• Status: Active Grant

• Current Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings), Regents of the University of California (University of California)
• Original Assignee: Sequenom Incorporated (Laboratory Corporation Of America Holdings), Regents of the University of California (University of California)
• Inventors: Braun, Andreas, Self, Christopher, Cantor, Charles R., Cook, Charles, Taylor, Susan, Burns-Hamuro, Lora, Kammerer, Stefan M., Olson, Gary
• Primary Examiner(s): PROUTY, REBECCA E
• Application Number:
  US10/428,254
• Publication Number:
  US 20030232420A1
• Time in Patent Office: 1,986 Days
• Field of Search: None
• US Class Current: 530/324
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/072 maintaining or altering function, i.e. knock in
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• CPC Class Codes: C07K 14/47 from mammals

Abstract

A-kinase anchor protein (AKAPs) muteins, peptides thereof, and nucleic acids encoding the peptides are provided herein. Also provided are transgenic animals, cells comprising transgenes and various methods employing such peptides.

Claims

1. A polypeptide that is a mutein of SEQ ID NO:

2, wherein the mutein exhibits modified binding to a regulatory subunit of PKA compared to SEQ ID NO;

2 and wherein said mutein;

is a peptide selected from the group consisting of a) a peptide having the sequence SEQ ID NO;

2, b) a peptide having the sequence SEQ ID NO;

2 further comprising a C-terminal cysteine, c) a peptide having the sequence SEQ ID NO;

2 wherein residues 1-8 are deleted, and d) a peptide having the sequence SEQ ID NO;

2 wherein residues 1-8 are deleted further comprising a C-terminal cysteine;

except that said peptide has an amino acid residue substitution at the residue equivalent to residue 21 of SEQ ID NO;

2 of Trp and/or Ile for Val, or an amino acid residue substitution at the residue equivalent to residue 12 of SEQ ID NO;

2 of Phe for Leu; and

zero, one, or two amino acid residue substitutions selected from the group consisting of Phe, Ile, Leu, Val, His, Met, Arg, Thr, Trp, or Tyr at the residue equivalent to residue 9 of SEQ ID NO;

2 for Gln; and

Phe, Ile, Leu, Thr, Val, Trp, or Tyr at the residue equivalent to residue 25 of SEQ ID NO;

2 for Met.

2. A polypeptide of claim 1, wherein the mutein exhibits modified binding to a regulatory subunit of PKA compared to a peptide having the sequence SEQ ID NO:

2.

3. The polypeptide of claim 1 that exhibits enhanced binding to PKA-RIα

subunits.

4. The polypeptide of claim 3 that exhibits normal or reduced binding to PKA-RIIα

subunits.

5. The polypeptide of claim 1 that exhibits reduced binding to PKA-RIIα

subunits.

6. The polypeptide of claim 5 that exhibits normal or increased binding to PKA-RIα

subunits.

7. The peptide of claim 1, wherein the peptide exhibits a preferred or exclusive binding to PKA-RIα

subunits relative to PKA-RIIα

subunits.

9. The mutein of claim 1, wherein said mutein comprises an amino acid substitution at residue 21 of Ile or Trp for Val.

10. The mutein of claim 1, wherein said mutein comprises an amino acid substitution at residue 21 of Trp for Val.

11. The mutein of claim 9, wherein said mutein comprises an amino acid substitution at residue 9 of Phe for Gln.

12. The mutein of claim 1, wherein said mutein is a peptide having the sequence SEQ ID NO:

2 wherein amino acids 1-8 are deleted or a peptide having the sequence SEQ ID NO;

2 wherein amino acids 1-8 are deleted further comprising a C-terminal cysteine.

13. The mutein of claim 9, wherein said mutein is a peptide having the sequence SEQ ID NO:

2 wherein amino acids 1-8 are deleted or a peptide having the sequence SEQ ID NO;

2 wherein amino acids 1-8 are deleted further comprising a C-terminal cysteine.

14. The mutein of claim 10, wherein said mutein is a peptide having the sequence SEQ ID NO:

2 wherein amino acids 1-8 are deleted or a peptide having the sequence SEQ ID NO;

2 wherein amino acids 1-8 are deleted further comprising a C-terminal cysteine.

17. The mutein of claim 1, wherein said mutein is

8. A peptide that has enhanced ability to bind to PKA-RIα

subunit, and a reduced ability to bind to PKA-RIIα

subunit, compared to the peptide of SEQ ID NOs;

1 or 2, wherein the peptide is selected from the group consisting of;

15. A peptide that has an enhanced ability to bind to PKA-RIα

subunit, and a reduced ability to bind to PKA-RIIα

subunit, compared to the peptide of SEQ ID NOs;

1 or 2, wherein the peptide is selected from the group consisting of;

16. A peptide that binds to the PKA-RIα

subunit but has substantially no ability to bind to the PKA-RIIα

subunit, compared to the peptide of SEQ ID NOs;

1 or 2, wherein the peptide is