Discrete PEG constructs
Disclosed are linear discrete PEG constructs, which can be created and produced in a precise and reproducible way. Key to being able to do these things, where x in the discrete PEG x can vary from about 2 to about 64, is that the processes used to make each linear portion is controlled to give essentially one oligomer/one compound. Having a variable length linear discrete PEG construct that is (a) primarily an linear discrete PEG construct with diagnostic or therapeutic groups attached along a chain of attachment cores, which is attached to a preferential locator; (b) is an m-discrete PEG as the terminal construct on the linear portion, and “hidden”; (c or linear discrete PEG with a terminus group that can be either negatively or positively charged, or neutral; and any of the discrete PEG portions can be designed to be cleaved after entering the cell.
1. A substantially pure construct represented by:
where,
(a) AC is an amino acid attachment core;
(b) the linear hydrocarbon chains ( ) contains a discrete PEG residue of between about 4 and 64 ethylene oxide residues;
(c) A is a chemically reactable group or a chemically reactive group;
(d) the terminal linear discrete PEG-containing chain ( ) has between about 8 and 72 ethylene oxide residues and having a terminal non-reactive moiety; and
(e) n ranges between 1 and 10;
where A is biorthogonal;
where A biorthogonal.
2. The substantially pure compound of claim 1 , wherein A is a cell surface and matrix antigen, transport protein, receptor protein, an antibody, antibody fragment, cytokine, aptamer, siRNA, vitamin, steroid, a nanoparticle, or microparticle.
3. The substantially pure compound of claim 1 , wherein the wavy line, , contains between about 4 and 48 ethylene oxide groups.
4. The substantially pure compound of claim 1 , wherein each solid line, , independently, contains between about 8 and 36 ethylene oxide groups.
5. The substantially pure compound of claim 4 , wherein the wavy line, , attached to AC contains, between about 4 and 48 ethylene oxide groups.
6. The substantially pure compound of claim 1 , where the non-reactive terminal moiety of the terminal linear discrete PEG-containing chain ( ) is a methoxy group.
7. The substantially pure compound of claim 1 , where the non-reactive terminal moiety of the terminal linear discrete PEG-containing chain ( ) is a charged group.
8. A substantially pure construct represented by:
where,
(a) AC is an amino acid attachment core;
(b) the linear hydrocarbon chains ( ) contain a discrete PEG residue of between about 4 and 64 ethylene oxide residues;
(c) G is a masked chemically reactive moiety;
(d) A is a chemically reactable group or a chemically reactive group;
(e) the terminal linear discrete PEG-containing chain ( )has between about 8 and 72 ethylene oxide residues and having a terminal non-reactive moiety; and
(f) n ranges between 1 and 10;
where A is biorthogonal; and
where A and G are independently reactive or reactable.
9. The substantially pure compound of claim 8 , wherein G is one or more of:
(a) a diagnostic group, being one or more of radiolabels, chromogenic and fluorescent dyes, a biotin, and combinations thereof; or
(b) a therapeutic group being one or more of radionuclides, toxic drugs, cytokines, enzymes, antibiotic, and combinations thereof.
10. The substantially pure compound of claim 8 , wherein A is a cell surface and matrix antigen, transport protein, receptor protein, an antibody, antibody fragment, peptide, peptide substrate, cytokine, aptamer, siRNA, vitamin, steroid, a nanoparticle, or microparticle.
11. The substantially pure compound of claim 8 , wherein G is one or more of:
(a) a diagnostic group, being one or more of radiolabels, chromogenic and fluorescent dyes, a biotin, and combinations thereof; or
(b) a therapeutic group being one or more of radionuclides, toxic drugs, cytokines, enzymes, antibiotic, and combinations thereof.
12. A substantially pure construct represented by:
where,
(a) AC is an amino acid attachment core;
(b) the linear hydrocarbon chains ( ) contains a discrete PEG residue of between about 4 and 64 ethylene oxide residues;
(c) A is a biologically active group;
(d) the terminal linear discrete PEG-containing chain ( )has between about 8 and 72 ethylene oxide residues and having a terminal non-reactive moiety; and
(e) n ranges between 1 and 10;
where A is biorthogonal.
13. A substantially pure construct represented by:
where,
(a) AC is an amino acid attachment core;
(b) the linear hydrocarbon chains ( ) contains a discrete PEG residue of between about 4 and 64 ethylene oxide residues;
(c) G is a biologically active group;
(d) A is a chemically reactable group or a chemically reactive group;
(e) the terminal linear discrete PEG-containing chain ( )has between about 8 and 72 ethylene oxide residues and having a terminal non-reactive moiety; and
(f) n ranges between 1 and 10;
where A biorthogonal; and
where A and G are independently reactive or reactable.