Method for site-specific polyvalent display on polymers
The present invention relates to novel complex peptidomimetic products comprising multiple homogeneous or heterogeneous pendant groups that are site-specifically positioned along a linear oligomer or polymer scaffold and methods of making thereof. More specifically, the invention relates to N-substituted glycine peptoid oligomers or peptoids and their use as substrates for azide-alkyne [3+2]-cycloaddition conjugation reactions and subsequent additional rounds of oligomerization and cycloaddition. The methods of the invention may also be used to generate peptoid-peptide hybrid or peptide products comprising multiple homogeneous or heterogeneous pendant groups, which are positioned precisely along the linear oligomer or polymer scaffold.
1. A linear oligomer comprising a plurality of identical backbone-attached pendant groups, wherein each of the identical backbone-attached pendant groups is attached to the backbone via a triazole linkage group.
2. The linear oligomer of claim 1 , wherein the oligomer comprises between 2-1,000 monomers.
3. The linear oligomer of claim 1 , wherein the oligomer comprises between 2-100 monomers.
4. The linear oligomer of claim 1 , wherein the oligomer comprises between 2-25 monomers.
5. The linear oligomer of claim 1 , wherein the oligomer is mono-valent, di-valent, tri-valent, tetra-valent, penta-valent, hexa-valent, hepta-valent, octa-valent, nona-valent, and deca-valent.
6. The linear oligomer of claim 1 , wherein the backbone-attached pendant groups comprise hormone receptor ligands, cell surface receptor ligands, tumor specific antigen ligands, cytotoxic agents, pharmaceutical moieties, fluorophores, chelates, radioisotopes, affinity tags, or antibiotic moieties.
7. The linear oligomer of claim 1 , wherein the backbone-attached pendant group is attached to the backbone via a triazole linkage group, and the triazole linkage group is formed by transformation of ethynyl or azido of the pendant group.
8. The linear oligomer of claim 7 , wherein the transformation of ethynyl or azido of the pendant group occurs via azide-alkyne [3+2]-cycloaddition conjugation.
9. A polyvalent linear oligomer of claim 1 , wherein the backbone-attached pendant groups comprise steroid hormone receptor ligands.
10. The linear oligomer of claim 1 , wherein the backbone-attached pendant groups comprise hormone receptor ligands, and the hormone receptor ligand is 17a-ethynyltestosterone, 17a-ethynylestrdiol, norgestimate, 17a-proynylestradiol, or 17a-butynylestradiol:
11. The linear oligomer of claim 1 , wherein the backbone-attached pendant groups comprise hormone receptor ligands, and each hormone receptor ligand is attached to the backbone via a triazole linkage which is formed through the transformation of the triple bond of the hormone receptor ligand.
12. The linear oligomer of claim 1 , wherein the backbone-attached pendant groups comprise hormone receptor ligands; each hormone receptor ligand is attached to the backbone via a triazole linkage which is formed via azide-alkyne [3+2]-cycloaddition conjugation.
13. The linear oligomer of claim 1 , wherein the pendant groups are selected from phenyl propargyl ether, (4-pentylphenyl)ethyne, (4-fluoro-3-methylphenyl)ethyne, 3-phenylpropyne, and ethynylferrocene; and each pendant group is attached to the backbone via a triazole linkage which is formed through the transformation of the triple bond of the pendant group.
14. The linear oligomer of claim 1 , wherein the pendant groups are selected from phenyl propargyl ether, (4-pentylphenyl)ethyne, (4-fluoro-3-methylphenyl)ethyne, 3-phenylpropyne, and ethynylferrocene; and each pendant group is attached to the backbone via a triazole linkage which is formed via azide-alkyne [3+2]-cycloaddition conjugation.
15. The linear oligomer of claim 1 , wherein the pendant groups are selected from
and each pendant group is attached to the backbone via a triazole linkage which is formed through the transformation of the azido group of the pendant group.
16. The linear oligomer of claim 1 , wherein the backbone comprises N-substituted glycine monomers.
17. The linear oligomer of claim 1 , wherein the backbone comprises N-substituted glycine monomers, and the substitution on the N is methoxyethyl, aminopropyl, aminobutyl, imidazoethyl, imidazomethyl, benzyl, phenethyl, naphthylmethyl, or guanidinopropyl.
18. The linear oligomer of claim 1 , wherein the polyvalent linear oligomer is
19. The linear oligomer of claim 1 , wherein the polyvalent linear oligomer is
and wherein n is 3 or 6.
20. The linear oligomer of claim 1 , wherein the polyvalent linear oligomer is
21. The linear oligomer of claim 1 , wherein the polyvalent linear oligomer is
and wherein n is 2, 3, 4, 5, 6, 7, 8, 9, or 10; and