title: Functional native disulfide bridging enables delivery of a potent, stable and targeted antibody-drug conjugate (ADC).
abstract: Herein we report the use of next generation maleimides (NGMs) for the construction of a potent antibody-drug conjugate (ADC) via functional disulfide bridging. The linker has excellent stability in blood serum and the ADC, armed with monomethyl auristatin E (MMAE), shows excellent potency and cancer cell selectivity in vitro.
authors.affiliation: Department of Chemistry, University College London, London, WC1H 0AJ, UK. j.r.baker@ucl.ac.uk v.chudasama@ucl.ac.uk.
authors.forename: João P M
authors.initials: JP
authors.lastname: Nunes
authors.forename: Maurício
authors.initials: M
authors.lastname: Morais
authors.forename: Vessela
authors.initials: V
authors.lastname: Vassileva
authors.forename: Eifion
authors.initials: E
authors.lastname: Robinson
authors.forename: Vineeth S
authors.initials: VS
authors.lastname: Rajkumar
authors.forename: Mark E B
authors.initials: ME
authors.lastname: Smith
authors.forename: R Barbara
authors.initials: RB
authors.lastname: Pedley
authors.forename: Stephen
authors.initials: S
authors.lastname: Caddick
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Vijay
authors.initials: V
authors.lastname: Chudasama
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D057930:Click Chemistry; D004220:Disulfides / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000633:toxicity; D061986:MCF-7 Cells; D009842:Oligopeptides / Q000737:chemistry*; D000068878:Trastuzumab / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D004220:Disulfides; D005456:Fluorescent Dyes; D018796:Immunoconjugates; D009842:Oligopeptides; D000068878:Trastuzumab; C495575:monomethyl auristatin E