Stably Tethered Structures of Defined Compositions with Multiple Functions or Binding Specificities

摘要

The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. The disclosed methods and compositions provide a simple, easy to purify way to obtain any binary compound attached to any monomeric compound, or any trinary compound.

主权项

1. A stably tethered structure comprising:
a) two copies of a first fusion protein comprising a dimerization and docking domain (DDD) selected from the group consisting of residues 1-44 of human protein kinase A RIIα and R11β fused to a first protein or peptide, wherein the first protein or peptide is a first antibody or antigen-binding fragment thereof; and b) one copy of a second fusion protein comprising the amino acid sequence selected from the group consisting of the anchoring domain (AD) of A-kinase anchoring protein (AKAP) fused to a second protein or peptide, wherein the second protein or peptide is a second antibody or antigen-binding fragment thereof;wherein the two copies of the DDD bind to the AD to form a stably tethered structure.