Antibody conjugates and methods of making the antibody conjugates

1. A method comprising:

modifying an antibody by reacting an antibody with a native EndoS or a mutant EndoS to form a modified antibody with a trimmed oligosaccharide;

glycosylating the modified antibody with an oligosaccharide using a mutant EndoS; and

attaching a first bioorthogonal reaction handle to the oligosaccharide, wherein the bioorthogonal reaction handle attached to the oligosaccharide is decasaccharide azide oxazoline having the following structure:

2. The method of claim 1 , further comprising attaching a payload molecule to the oligosaccharide, where the payload molecule has a second bioorthogonal reaction handle, where attaching the payload molecule comprises:

attaching the first bioorthogonal reaction handle to the second bioorthogonal reaction handle.

3. The method of claim 2 , wherein the payload molecule is at least one compound selected from the group consisting of: any small molecule, DNA, RNA, amino acid, peptide, polypeptide, antibody, aptamer, ribozyme, guide sequence for a ribozyme that inhibits translation or transcription of an essential tumor proteins or gene, hormone, immunomodulator, antipyretic, anxiolytic, antipsychotic, analgesic, antispasmodic, anti-inflammatory, anti-histamine, anti-infective, radiolabel, fluorophore, imaging agent, and chemotherapeutic.

4. The method of claim 2 , further comprising attaching a second linker between the payload molecule and the second bioorthogonal reaction handle.

5. The method of claim 1 , further comprising attaching a first linker between the first bioorthogonal reaction handle and the oligosaccharide.

6. The method of claim 1 , wherein the antibody is Herceptin.

7. The method of claim 2 , wherein the second bioorthogonal reaction handle attached to the payload molecule selectively reacts and attaches to the first reaction attached to the oligosaccharide on the modified antibody.

8. The method of claim 5 , wherein the first linker is selected from the group consisting of amides, hydrazones, disulfides, thioethers and peptides.

9. The method of claim 4 , wherein the second linker is selected from the group consisting of amides, hydrazones, disulfides, thioethers and peptides.

10. The method of claim 4 , wherein the second bioorthogonal reaction handle is selected from the group consisting of strained alkynes, cyclopropenes, nitrile oxides, nitrile imines, strained alkenes and nonbornenes.

11. The method of claim 1 , wherein the first bioorthogonal reaction handle is attached to the oligosaccharide via an amidation reaction.