Peptides whose uptake in cells is controllable

Patent metadata

Field	Value
Publication number	US-9682151-B2
Application number	US-201013384591-A
Country	US
Kind code	B2
Filing date	Jul 15, 2010
Priority date	Jul 15, 2009
Publication date	Jun 20, 2017
Grant date	Jun 20, 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)-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 glutamates; 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 comprising a structure (A-X-B-C)-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 a sequence of PLG-C(me)-AG; and
M is a macromolecular carrier;
wherein M is bound to A or B, and C(me) is S-methylcysteine.

2. The molecule of claim 1 , wherein A and B comprise D-amino acids.

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

4. The molecule of claim 1 , wherein C is an indocarbocyanine dye.

5. The molecule of claim 1 , wherein C is an indocarbocyanine dye, Cy5, Cy5.5, Cy7, IRDYE 800CW, ALEXA647, or a combination thereof.

6. The molecule of claim 5 , wherein C is Cy5.

7. The molecule of claim 6 , wherein Cy5 further comprises a D-cysteine which attaches Cy5 to B.

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

9. A method of imaging a tumor in a subject, comprising imaging the tumor after the subject has been administered a molecule of the structure (A-X-B-C)-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 a sequence of PLG-C(me)-AG; and
M is a macromolecular carrier;
wherein M is bound to A or B, and C(me) is S-methylcysteine.

10. A method of imaging surgical margins for a tumor or tissue resection in a subject, comprising imaging the surgical margins after the subject has been administered a molecule of the structure (A-X-B-C)-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 a sequence of PLG-C(me)-AG; and
M is a macromolecular carrier;
wherein M is bound to A or B, and C(me) is S-methylcysteine.

11. A method of removing a tumor in a subject, comprising removing the tumor after the subject has been administered a molecule of the structure (A-X-B-C)-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 a sequence of PLG-C(me)-AG; and
M is a macromolecular carrier; and
wherein M is bound to A or B, and C(me) is S-methylcysteine.

Assignees

• Tsien Roger
• Aguilera Todd
• Olson Emilia
• Jiang Tao
• Nguyen Quyen
• Univ California

Inventors

• Tsien Roger
• Aguilera Todd
• Olson Emilia
• Jiang Tao
• Nguyen Quyen

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/62

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

• C07K7/06

  having 5 to 11 amino acids · CPC title

• A61K47/6911

  the form being a liposome · CPC title