Multifunctional linker technology containing an N4 group
In some aspects, the present disclosure provides compositions comprising an N4-based MMC ligand, a cell targeting group, and a fluorophore or a therapeutic compound comprising a formula: wherein the variables are as defined herein. In some embodiments, these compositions may be used in the imaging techniques or in the treatment of a disease or disorder such as cancer.
1. A compound of the formula:
wherein:
two of R 1 , R 2 , R 3 , and R 4 are -A-COR 5 , wherein:
A is alkanediyl (C≤8) or substituted alkanediyl (C≤8) ; and
R 5 is hydroxy, alkoxy (C≤8) , or substituted alkoxy (C≤8) ;
one of R 1 , R 2 , R 3 , or R 4 is a peptide group, wherein the peptide group comprises a conjugated antibody that comprises a light and heavy variable region;
one of R 1 , R 2 , R 3 , and R 4 is a fluorophore group or
a chemotherapeutic group; and
M is a metal atom of any oxidation state or absent;
or a pharmaceutically acceptable salt thereof, wherein:
R 5 is alkoxy (C≤8) ; or
R 4 is a chemotherapeutic group.
2. The compound of claim 1 , wherein R 5 is hydroxy.
3. The compound of claim 1 , wherein R 5 is alkoxy (C≤8) .
4. The compound of claim 1 , wherein the peptide group further comprises a linker which joins the peptide to formula I.
5. The compound of claim 1 , wherein R 2 is the peptide group that comprises the conjugated antibody and R 4 is a fluorophore group or chemotherapeutic group.
6. The compound of claim 5 , wherein the peptide group further comprises a linker which joins the antibody to formula I.
7. The compound of claim 1 , wherein R 4 is a chemotherapeutic group.
8. The compound of claim 7 , wherein the chemotherapeutic group further comprises a linker which joins the chemotherapeutic compound to formula I.
9. The compound of claim 7 , wherein the chemotherapeutic group is further defined by the formula:
10. The compound of claim 1 , wherein R 4 is a fluorophore group.
11. The compound of claim 10 , wherein the fluorophore group is further defined by the formula:
12. The compound of claim 10 , wherein the fluorophore group further comprises a linker which joins the fluorophore to formula I.
13. The compound of claim 12 , wherein the fluorophore is further defined by the formula:
14. The compound of claim 1 , wherein M is a transition metal atom.
15. The compound of claim 1 , further defined as:
wherein:
and
R b is the peptide group that comprises the conjugated antibody;
or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising:
(a) the compound of claim 1 ; and
(b) a pharmaceutically acceptable carrier.
17. A method of delivering a compound or composition of claim 1 to a cell comprising contacting the cell with the compound or composition.