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Review
. 2015 Jun 1;12(6):1848-62.
doi: 10.1021/acs.molpharmaceut.5b00082. Epub 2015 May 21.

Antibody conjugates with unnatural amino acids

Trevor J Hallam  1 , Erik Wold  2 , Alan Wahl  3 , Vaughn V Smider  2
Affiliations
Review

Antibody conjugates with unnatural amino acids

Trevor J Hallam et al. Mol Pharm. .

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.

Keywords: Chinese hamster ovary; antibody−drug conjugate; drug:antibody ratio; heavy chain; light chain; pharmacokinetics; tRNA synthetase; unnatural amino acid.

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