Optimisation of the dibromomaleimide (DBM) platform for native antibody conjugation by accelerated post-conjugation hydrolysis. Issue 14 (14th March 2017)

• Record Type: Journal Article
• Authors: Morais, Maurício; Nunes, João P. M.; Karu, Kersti; Forte, Nafsika; Benni, Irene; Smith, Mark E. B.; Caddick, Stephen; Chudasama, Vijay; Baker, James R.
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 14(2017)
• Page Start: 2947
• Page End: 2952
• Publication Date: 2017-03-14
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob00220c
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Dibromomaleimide (DBM) reagents are described which hydrolyse rapidly post-conjugation, representing an optimised platform for homogeneous and stable antibody conjugation. Abstract : Disulfide bridging offers a convenient approach to generate site-selective antibody conjugates from native antibodies. To optimise the reagents available to achieve this strategy, we describe here the use of dibromomaleimides designed to undergo accelerated post-conjugation hydrolysis. Conjugation and hydrolysis, which serve to 'lock' the conjugates as robustly stable maleamic acids, is achieved in just over 1 h. This dramatic acceleration is also shown to infer significant improvements in homogeneity, as demonstrated by mass spectrometry analysis.