Peptides whose uptake in cells is controllable

Patent metadata

Field	Value
Publication number	US-9808532-B2
Application number	US-201013384581-A
Country	US
Kind code	B2
Filing date	Jul 15, 2010
Priority date	Jul 15, 2009
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A-X-B-C)n-M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutatmates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.

First claim

What is claimed is:

1. A molecule having the formula: (A-X-B-C) n -M wherein:
C is a fluorescent moiety;
A is a peptide with a sequence comprising a series of 5 glutamate residues;
B is a peptide with a sequence comprising a series of 8 arginine residues;
X is a cleavable linker comprising PRSFL (SEQ ID NO: 22);
M is a macromolecular carrier; and
n is an integer between 1 and 20;
wherein M is bound to A or B.

2. The molecule of claim 1 , wherein X is further attached to 6-aminohexanoyl, 5-amino-3-oxapentanoyl, or a combination thereof.

3. The molecule of claim 1 , wherein X comprises a sequence selected from: DPRSFL (SEQ ID NO: 1), or PPRSFL (SEQ ID NO: 2).

4. The molecule of claim 1 , wherein M is a macromolecular carrier selected from: a dendrimer, dextran, a PEG polymer, or albumin.

5. The molecule of claim 1 , wherein M is a PEG polymer.

6. The molecule of claim 1 , wherein the fluorescent moiety is an indocarbocyanine dye.

7. The molecule of claim 1 , wherein the fluorescent moiety is selected from Cy5, Cy5.5, Cy7, Alexa 647, IRDYE 800CW, or a combination thereof.

8. The molecule of claim 1 , wherein the fluorescent moiety is an MRI contrast agent.

9. A method of imaging thrombin activity in a subject, comprising imaging thrombin activity after the subject has been administered a molecule of the structure (A-X-B-C) n -M, wherein
C is a fluorescent moiety;
A is a peptide with a sequence comprising a series of 5 glutamate residues;
B is a peptide with a sequence comprising a series of 8 arginine residues;
X is a cleavable linker comprising PRSFL (SEQ ID NO: 22);
M is a macromolecular carrier; and
n is an integer between 1 and 20;
wherein M is bound to A or B.

10. The method of claim 9 , wherein the fluorescent moiety is an indocarbocyanine dye.

11. The method of claim 9 , wherein the fluorescent moiety is selected from Cy5, Cy5.5, Cy7, Alexa 647, IRDYE 800CW, or a combination thereof.

Assignees

• Tsien Roger
• Olson Emilia
• Jiang Tao
• Nguyen Quyen
• Whitney Michael
• Univ California

Inventors

• Tsien Roger
• Olson Emilia
• Jiang Tao
• Nguyen Quyen
• Whitney Michael

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61K47/6911

  the form being a liposome · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K49/0056

  Peptides, proteins, polyamino acids · CPC title