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Antibody conjugates with unnatural amino acids

Academic Article
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Overview

related to degree

  • Wold, Erik, Ph.D. in Chemistry, Scripps Research 2009 - 2015

authors

  • Hallam, T. J.
  • Wold, Erik
  • Wahl, A.
  • Smider, Vaughn

publication date

  • June 2015

journal

  • Molecular Pharmaceutics  Journal

abstract

  • Antibody conjugates are important in many areas of medicine and biological research, and antibody-drug conjugates (ADCs) are becoming an important next generation class of therapeutics for cancer treatment. Early conjugation technologies relied upon random conjugation to multiple amino acid side chains, resulting in heterogeneous mixtures of labeled antibody. Recent studies, however, strongly support the notion that site-specific conjugation produces a homogeneous population of antibody conjugates with improved pharmacologic properties over randomly coupled molecules. Genetically incorporated unnatural amino acids (uAAs) allow unique orthogonal coupling strategies compared to those used for the 20 naturally occurring amino acids. Thus, uAAs provide a novel paradigm for creation of next generation ADCs. Additionally, uAA-based site-specific conjugation could also empower creation of additional multifunctional conjugates important as biopharmaceuticals, diagnostics, or reagents.

subject areas

  • Amino Acids
  • Animals
  • Antibodies
  • Humans
  • Immunoconjugates
  • Protein Structure, Secondary
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Research

keywords

  • Chinese hamster ovary
  • antibody-drug conjugate
  • drug antibody ratio
  • heavy chain
  • light chains
  • pharmacokinetics
  • tRNA synthetase
  • unnatural amino acid
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Identity

International Standard Serial Number (ISSN)

  • 1543-8384

Digital Object Identifier (DOI)

  • 10.1021/acs.molpharmaceut.5b00082

PubMed ID

  • 25898256
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Additional Document Info

start page

  • 1848

end page

  • 1862

volume

  • 12

issue

  • 6

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