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Development and Applications of Well-Defined Antibody and Antibody Fragment Bioconjugates

  • Author(s): Netirojjanakul, Chawita
  • Advisor(s): Francis, Matthew B.
  • et al.
Abstract

Antibodies have been widely used in many biological applications, including reseach tools, imaging, and therapeutics, due to their excellent binding specificity and affinity. As therapeutics, the ability to elicit immune effector functions and plasma half-life extension through the function of the constant domain (Fc) render antibodies superior to small molecules in these aspects. This work describes the use of chemical-based bioconjugation techniques to develop novel bioconjugates from antibody fragments and full-sized antibodies for therapeutic and imaging purposes. The complex structures of this class of biomolecules -- with the presence of multiple polypeptide chains, extensive disulfide networks, and critically important glycosylation patterns -- make it difficult to manipulate these biomolecules in a controlled manner. Thus, protein modification techniques play important roles in enabling the development of these constructs. In this work, we discuss the generation of Fc-synthetic molecule hybrids as antibody mimics, full-sized antibody-synthetic molecule conjugates as bispecific antibodies, and MS2-antibody conjugates as targeted delivery vehicles. The ability to conjugate different moieties into one molecule provides the ability to shuffle and combine synergistic advantages of the component molecules.

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