Peptide nucleic acid based guanidinium compounds
Disclosed herein are transmembrane transporter compounds containing guanidinium groups to enhance transport of a polymer backbone across biomembranes. Therapeutic and other biologically active moieties may be attached to the compounds. The polymer backbone may include peptide nucleic acid monomer units.
1. A compound having the formula:
wherein:
each L is independently selected to be a linker moiety comprising a molecular fragment having a molecular weight less than about 1000 or L is absent; and
each T is a terminal group independently selected from the group consisting of hydrogen, hydroxy, an amine group, a carboxylic group, a N-terminal peptide, a C-terminal peptide, a reporting moiety, a targeting moiety, and a therapeutic moiety, or each T may be independently absent.
2. A compound having the formula:
wherein:
each L is independently selected to be a linker moiety comprising a molecular fragment having a molecular weight less than about 1000 or L is absent; and
each T is a terminal group independently selected from the group consisting of hydrogen, hydroxy, an amine group, a carboxylic group, a N-terminal peptide, a C-terminal peptide, a reporting moiety, a targeting moiety, and a therapeutic moiety, or each T may be independently absent.
3. A method for enhancing transport of a biologically active moiety across a biological membrane, comprising contacting a biological membrane with a compound of claim 1 or claim 2 , wherein at least one T comprises a moiety selected from the group consisting of a reporting moiety, a targeting moiety, and a therapeutic moiety, whereby said contacting is effective to promote transport of said compound across said biological membrane at a rate that is greater than a trans-membrane transport rate of the moiety in non-conjugated form.
4. The method of claim 3 , wherein said biological membrane is a eukaryotic cell membrane.
5. The method of claim 4 , wherein the eukaryotic cells selected from the group consisting of mammalian cells, cancer cells, insect cells, plant cells, and yeast cells.
6. The method of claim 3 , wherein said biological membrane is a prokaryotic cell membrane.
7. The method of claim 3 , wherein said biological membrane is a cancer cell membrane.
8. The method of claim 3 , wherein at least one T comprises a therapeutic moiety.
9. The method of claim 8 , wherein said therapeutic moiety is an anti-cancer agent.
10. A pharmaceutical composition, comprising a compound of claim 1 or claim 2 and a pharmaceutically acceptable carrier, diluent, or excipient.