Method and composition for biocatalytic protein-oligonucleotide conjugation and protein-oligonucleotide conjugate

A composition, comprising:

• a conjugate reaction product of:
• a fused sterol or stanol ring system, having a nucleophilic group at the 3-position of an A-ring of the fused sterol or stanol ring system with beta or alpha stereochemistry;
• a polypeptide, covalently linked through a C-terminal electrophilic residue to the fused sterol or stanol ring system;
• and
• an oligonucleotide attached through a linker to the fused sterol or stanol ring system.

A composition, comprising a conjugate reaction product of:

• a polypeptide having a C-terminal electrophilic residue,
• a fused sterol or stanol ring system, having a nucleophilic group at the 3-position of an A-ring of the fused sterol or stanol ring system with beta or alpha stereochemistry, covalently linked to the C-terminal electrophilic residue, and
• an oligonucleotide attached through a linker to a ring of the fused sterol or stanol ring system,
• prepared by a method comprising:
• providing a precursor polypeptide;
• providing the oligonucleotide attached through the linker to the ring of the fused sterol or stanol ring system;
• providing a protein catalyst adapted to link the precursor polypeptide to the steroylated or stanoylated-nucleic acid through a sterol or stanol moiety of the steroylated or stanoylated-nucleic acid;
• and
• reacting the steroylated or stanoylated-nucleic acid and the precursor polypeptide, catalyzed by the protein catalyst, to form the composition.