p53-BAD fusion proteins

Patent metadata

Field	Value
Publication number	US-11299526-B2
Application number	US-201916414683-A
Country	US
Kind code	B2
Filing date	May 16, 2019
Priority date	May 16, 2018
Publication date	Apr 12, 2022
Grant date	Apr 12, 2022

Abstract

Disclosed are peptides comprising a p53 peptide and a BH3-only protein. In some aspects, wherein the BH3-only protein is BAD, BID, BIM, NOXA. Disclosed are nucleic acid sequences comprising a sequence capable of encoding a p53 peptide operably linked to a nucleic acid sequence capable of encoding a BH3-only protein. Disclosed are nucleic acid sequences comprising a sequence capable of encoding one or more of the peptides disclosed herein. Disclosed are vectors comprising a nucleic acid sequence, wherein the nucleic acid sequence is capable of encoding one or more of the peptides disclosed herein. Also disclosed are methods of using the disclosed peptides, nucleic acid sequences, and vectors.

First claim

We claim:

1. A peptide comprising a p53 peptide and BAD, wherein the p53 is N-terminal to the BAD.

2. The peptide of claim 1 , wherein BAD comprises the amino acid sequence of

(SEQ ID NO: 1)

MFQIPEFEPSEQEDSSSAERGLGPSPAGDGPSGSGKHHRQA

PGLLWDASHQQEQPTSSSHHGGAGAVEIRSRHSSYPAGTED

DEGMGEEPSPFRGRSRSAPPNLWAAQRYGRELRRMSDEFVD

SFKKGLPRPKSAGTATQMRQSSSWTRVFQSWWDRNLGRGSS

APSQ.

3. The peptide of claim 1 , wherein BAD is a mutated BAD.

4. The peptide of claim 3 , wherein the mutated BAD has a serine to alanine substitution at one or more of positions 75, 99, and 118 of SEQ ID NO:1.

5. The peptide of claim 3 , wherein the mutated BAD has a serine to alanine substitution at positions 75 and 99 of SEQ ID NO:1.

6. The peptide of claim 5 , wherein the mutated BAD has an amino acid sequence of

(SEQ ID NO: 2)

MFQIPEFEPSEQEDSSSAERGLGPSPAGDGPSGSGKHHRQA

PGLLWDASHQQEQPTSSSHHGGAGAVEIRSRHSAYPAGTED

DEGMGEEPSPFRGRSRAAPPNLWAAQRYGRELRRMSDEFVD

SFKKGLPRPKSAGTATQMRQSSSWTRVFQSWWDRNLGRGSS

APSQ.

7. The peptide of claim 1 , wherein the p53 peptide is a full length p53.

8. The peptide of claim 1 , wherein the p53 peptide is a partial p53 peptide, wherein the partial p53 peptide retains pro-apoptotic function.

9. The peptide of claim 1 , further comprising a linker between the p53 peptide and BAD.

10. The peptide of claim 9 , wherein the linker is (GGGGS) 3 (SEQ ID NO:9), (PAPAPA) 3 (SEQ ID NO:10), (EAAAK) 3 (SEQ ID NO:11), or [LEA(EAAAK) 4 ] 2 LE (SEQ ID NO:12).

11. The peptide of claim 8 , wherein the partial p53 peptide consists of the DNA binding domain of p53.

12. The peptide of claim 8 , wherein the partial p53 peptide consists of amino acids 102-292 of SEQ ID NO:3.

13. The peptide of claim 8 , wherein the partial p53 peptide comprises the DNA binding domain of p53.

14. The peptide of claim 8 , wherein the partial p53 peptide further comprises a MDM2 binding domain, a proline-rich domain, a tetramerization domain, or a transactivation domain of p53.

15. A nucleic acid sequence comprising a sequence capable of encoding a p53 peptide operably linked to a nucleic acid sequence capable of encoding BAD, wherein the sequence capable of encoding a p53 peptide is 5′ to the sequence capable of encoding BAD.

Assignees

• Univ Utah Res Found

Inventors

• Lim Carol S
• Lu Phong

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/4746

  p53 · CPC title

• A61K38/00

  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 title

• C07K14/4747 Primary

  Apoptosis related proteins · CPC title