Prominin-1 peptide fragments and uses thereof
Described herein are peptide compositions of a prominin-1, which have regenerative activity. As such the peptides are useful when regeneration is needed, for example, to enhance angiogenesis, increase VEGF binding to endothelial cells, promote vasodilation, enhance cell migration, enhance cell proliferation, stimulate neuronal growth, prevent neurodegeneration, and/or promote neuroregeneration.
1. An isolated peptide comprising an amino acid sequence selected from the group consisting of:
LCGNSFSGGQPS (SEQ ID NO: 4);
PNIIPVLDEIKS (SEQ ID NO: 5);
LCGVCGYDRHAT (SEQ ID NO: 6);
DRVQRQTTTVVA (SEQ ID NO: 8);
CSFAYDLEAKANSLPPGNLRN (SEQ ID NO: 9);
and DRVQBQTTTVVA (SEQ ID NO: 54), wherein B is any one of the naturally occurring amino acids;
and wherein the isolated peptide is no more than 50 amino acids in length.
2. The isolated peptide of claim 1 , wherein said isolated peptide is constructed into a cyclic peptide.
3. The cyclic peptide of claim 2 , wherein the cyclic peptide comprises a formula of CX(DRVQBQTTTVVA)ZC (SEQ ID NO: 51) or ACX(DRVQBQTTTVVA)ZC (SEQ ID NO: 52), wherein X or Z are each independently 0-20 amino acids, and wherein B is any one of the naturally occurring amino acids.
4. The cyclic peptide of claim 3 , wherein the glutamine (Q) at position 6 of the core (DRVQBQTTTVVA) (SEQ ID NO: 54) of the cyclic peptide is substituted with any one of the known 20 amino acids other that glutamine.
5. The isolated peptide of claim 2 , wherein the cyclic peptide is selected from the group consisting of: ACGG(DRVQRQTTTVVA)GGC (SEQ ID NO: 15), ACGG(DRVQRQTTTVVA)GGGGGGC (SEQ ID NO: 16), and CGGGGGG(DRVQRQTTTVVA)GGCA (SEQ ID NO: 17).
6. The isolated peptide of claim 1 , wherein the peptide is conjugated to a polymer.
7. A fusion protein comprising the isolated peptide of claim 1 , fused to a heterologous peptide or polypeptide, wherein the fusion protein is not a full-length prominin-1.
8. A composition comprising a pharmaceutically acceptable carrier and an isolated peptide of claim 1 or fusion protein of claim 7 .
9. A method of promoting angiogenesis in a tissue in need thereof, the method comprising contacting said tissue with a composition of claim 8 .
10. The method of claim 9 , wherein the method is applied in the context of promoting wound healing, neuronal growth, protection or repair, tissue repair, bone repair, fertility promotion, cardiac hypertrophy, treatment of erectile dysfunction, modulation of blood pressure, revascularization after disease or trauma, tissue grafts, or tissue engineered constructs.
11. The isolated peptide of claim 1 , wherein the isolated peptide is no more than 30 amino acids in length.
12. An isolated peptide of claim 1 that comprises an amino acid substitution at one or more of positions 2, 3, 4, 5, 6, 7 or 12 of DRVQRTTTVVA (SEQ ID NO: 8) or one or more of positions 1, 3, 8, or 9 of LCGNSFSGGQPS (SEQ ID NO: 4).
13. An isolated peptide comprising an amino acid sequence consisting of:
ITNNTSSVIIEE (SEQ ID NO: 7), wherein the isolated eptide is no more than 25 amino acids in length.