N-terminal α-amino group modification of antibodies using a site-selective click chemistry method. Issue 5 (4th July 2018)

• Record Type: Journal Article
• Authors: Li, De-zhi; Han, Bing-nan; Wei, Rui; Yao, Gui-yang; Chen, Zhizhen; Liu, Jie; Poon, Terence C.W.; Su, Wu; Zhu, Zhongyu; Dimitrov, Dimiter S.; Zhao, Qi
• Is Part Of: MAbs. Volume 10:Issue 5(2018)
• Page Start: 712
• Page End: 719
• Publication Date: 2018-07-04
• Subjects: antibody -- antibody engineering -- antibody-drug conjugate -- click chemistry -- Site-specific modification,; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2018.1463122
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: Site-specific conjugation of small molecules to antibody molecules is a promising strategy for generation of antibody-drug conjugates. In this report, we describe the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2-pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively reacted with N-terminal amino groups of peptides and antibodies. In addition, the azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site-specific conjugation without requiring genetic engineering of peptides or antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability to modify proteins in a single step under physiological conditions that are sufficiently moderate to retain protein function. Therefore, this new click chemistry-based method could be a useful complement to other conjugation methods.