05-05-2016 дата публикации
Номер: US20160122391A1
The invention is directed to β-defensin-derived peptides and their use in modulating the activity of hematopoietic cells, particularly hematopoietic stem cells and progenitor cells. Specifically, the invention provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells. The invention further provides compositions and methods useful in the treatment of cancer. 1. A cyclized peptide selected from the group consisting of:(a) 1,10-cyclo[RGRKCCRRKK], (cTL-1, SEQ ID NO: 3), wherein the arginine at position 1 is linked through a peptide bond to the lysine at position 10; and(b) a cyclized homolog of SEQ ID NO: 3 having at least 70% sequence homology to SEQ ID NO: 3 and at least 70% identity with regard to the overall positive charge density of SEQ ID NO: 3, wherein the N-terminus and the C-terminus of the peptide are linked through a covalent bond, and wherein the two adjacent cysteines at positions 5 and 6 of SEQ ID NO: 3 are retained.2. The peptide of claim 1 , wherein the homolog has at least 70% of the hydrophilicity/hydrophobicity characteristics of SEQ ID NO: 3.3. The peptide of claim 1 , wherein the peptide is cTL-1 (SEQ ID NO: 3).4. A pharmaceutical composition containing an effective amount of the peptide of claim 1 , and one or more pharmaceutically accepted carriers claim 1 , excipients or diluents.5. A method for reducing or inhibiting cancer metastasis in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a peptide as set forth in .6. The method of claim 5 , wherein the subject is afflicted with a tumor characterized by CXCR5 expression of at least a portion of the tumor cells.7. The method of claim 6 , wherein the tumor is of hematopoietic origin.8. The method of claim 6 , wherein the tumor is leukemia.9. The method of claim 5 , wherein the homolog has at least 70% of the hydrophilicity/hydrophobicity characteristics of SEQ ID NO: 3.10. ...
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