Homogeneous antibody-drug conjugates via site-selective disulfide bridging.

Nafsika Forte, Vijay Chudasama, James R Baker

Journal: Drug discovery today. Technologies 2019;30():11-20

PMID: 30553515

Full Text on Elsevier Science View on PubMed

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.

Address: Department of Chemistry, University College London, London, UK.; Department of Chemistry, University College London, London, UK. Electronic address: [email protected].; Department of Chemistry, University College London, London, UK. Electronic address: [email protected].

DOI: 10.1016/j.ddtec.2018.09.004

Link outs

Free resources

Other Literature Sources:

https://www.lens.org/lens/search/patent/list?q=ref...

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S1740...

MeSH Terms: Disulfides, Humans, Immunoconjugates, Structure-Activity Relationship