Acid-cleavable thiomaleamic acid linker for homogeneous antibody-drug conjugation.
In this communication we describe a novel acid-cleavable linker strategy for antibody-drug conjugation. Functional disulfide bridging of the single interchain disulfide bond of a trastuzumab Fab fragment yields a homogeneous antibody-drug conjugate bearing a thiomaleamic acid linker. This linker is stable at physiological pH and temperature, but quantitatively cleaves at lysosomal pH to release the drug payload.
Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK.
Lourdes
L
Castañeda
Antoine
A
Maruani
Felix F
FF
Schumacher
Enrique
E
Miranda
Vijay
V
Chudasama
Kerry A
KA
Chester
James R
JR
Baker
Mark E B
ME
Smith
Stephen
S
Caddick
D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008298:Maleates / Q000737:chemistry*; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013696:Temperature; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D004220:Disulfides; D008298:Maleates; D004364:Pharmaceutical Preparations; C587403:thiomaleamic acid; D000068878:Trastuzumab