Conjugates of membrane translocating agents and pharmaceutically active agents
Membrane translocation peptides, compositions comprising them, chimeric molecules comprising them, and methods of using them to achieve transmembrane transport of various agents.
1. A composition comprising a translocating peptide, wherein said translocating peptide is a transport peptide or an extended peptide comprising said transport peptide, wherein said transport peptide is a retroinverted peptide and wherein the retroinverted peptide comprises a d-form amino acid sequence selected from the group consisting of a peptide of SEQ ID NOS:85 and 95-103 and the retroinverted sequence of SEQ ID NO:120.
2. The composition of claim 1 , wherein the transport peptide is partially or completely cyclic.
3. The composition of claim 1 , wherein the transport peptide is completely cyclic.
4. The composition of claim 1 , wherein the carboxyl end group of the translocating peptide has been modified to create an amide group.
5. A chimeric polypeptide comprising (A) a translocating peptide selected from the group consisting of a transport peptide, an extended peptide comprising said transport peptide, and a transport-active fragment of at least 4 contiguous amino acids of said transport peptide, wherein said transport peptide is a retroinverted peptide and wherein the retroinverted peptide comprises a d-form amino acid sequence selected from the group consisting of a peptide of SEQ ID NOS:85 and 95-103 and the retroinverted sequence of SEQ ID NO:120, (B) a translocatable peptide, and (C) an amino acid linker sequence that directly links the translocating peptide to the translocatable peptide, wherein said translocatable peptide is between 3 and 200 amino acids, and wherein said amino acid linker sequence is between 1 and 20 amino acids.
6. The chimeric peptide of claim 5 wherein said translocatable peptide is between 3 and 30 amino acids.
7. The chimeric peptide of claim 5 wherein the translocatable peptide is an opioid peptide.
8. The chimeric peptide of claim 5 wherein said linker sequence is not more than 7 amino acids.
9. A composition comprising a translocating peptide, said translocating peptide selected from the group consisting of a transport peptide, an extended peptide comprising said transport peptide, and a transport-active fragment of at least 4 contiguous amino acids of said transport peptide, wherein said transport peptide a retroinverted peptide and wherein the retroinverted peptide comprises a d-form amino acid sequence selected from the group consisting of a peptide of SEQ ID NOS:85 and 95-103 and the retroinverted sequence of SEQ ID NO:120, and wherein said transport peptide is partially or completely cyclic.
10. A composition comprising a translocating peptide, said translocating peptide selected from the group consisting of a transport peptide, an extended peptide comprising said transport peptide, and a transport-active fragment of at least 4 contiguous amino acids of said transport peptide, wherein said transport peptide a retroinverted peptide and wherein the retroinverted peptide comprises a d-form amino acid sequence selected from the group consisting of a peptide of SEQ ID NOS:85 and 95-103 and the retroinverted sequence of SEQ ID NO:120, and wherein said transport-active fragment is partially or completely cyclic.
11. The composition of claim 9 , wherein said transport peptide is completely cyclic.
12. The composition of claim 10 , wherein said transport-active fragment is completely cyclic.