Homogeneous antibody-drug conjugates via site-selective disulfide bridging. (December 2018)

• Record Type: Journal Article
• Authors: Forte, Nafsika; Chudasama, Vijay; Baker, James R.
• Is Part Of: Drug discovery today. Volume 30(2018)
• Page Start: 11
• Page End: 20
• Publication Date: 2018-12
• Subjects: Drug development -- Periodicals; Physiology, Pathological -- Periodicals; Drugs -- Design -- Periodicals; 615.1
• DOI: 10.1016/j.ddtec.2018.09.004
• Languages: English
• ISSNs: 1740-6749

Abstract

Abstract : Antibody-drug conjugates (ADCs) constructed using site-selective labelling methodologies are likely to dominate the next generation of these targeted therapeutics. To this end, disulfide bridging has emerged as a leading strategy as it allows the production of highly homogeneous ADCs without the need for antibody engineering. It consists of targeting reduced interchain disulfide bonds with reagents which reconnect the resultant pairs of cysteine residues, whilst simultaneously attaching drugs. The 3 main reagent classes which have been exemplified for the construction of ADCs by disulfide bridging will be discussed in this review; bissulfones, next generation maleimides and pyridazinediones, along with others in development.