Dear Editor,The selection of linkers and payloads plays a crucial role in determining the therapeutic indices of antibody–drug conjugates(ADCs).1 Valine–citrulline(Val–Cit)coupled with a self-immolativeρ-aminobenz...Dear Editor,The selection of linkers and payloads plays a crucial role in determining the therapeutic indices of antibody–drug conjugates(ADCs).1 Valine–citrulline(Val–Cit)coupled with a self-immolativeρ-aminobenzyl(PAB)spacer as a cleavable dipeptide linker,designated as“VC linker”in this letter,has been popularly used in ADC conjugation.1 However,VC linker is highly hydrophobic2 and,together with hydrophobic payloads at high DARs(drug-toantibody ratios),may turn ADC molecules that have hydrophilic parts in their antibody portions,into aggregation-prone“surfactant-like”structures.展开更多
基金supported by the China National Grand S&T Special Project(2019ZX09732002-006)the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDA12020223 and XDA12020330)+1 种基金the National Natural Science Foundation of China(81872785 and 81673347)Shanghai Municipal Commission of Science and Technology of China(17431904400 and 19YF1457400)。
文摘Dear Editor,The selection of linkers and payloads plays a crucial role in determining the therapeutic indices of antibody–drug conjugates(ADCs).1 Valine–citrulline(Val–Cit)coupled with a self-immolativeρ-aminobenzyl(PAB)spacer as a cleavable dipeptide linker,designated as“VC linker”in this letter,has been popularly used in ADC conjugation.1 However,VC linker is highly hydrophobic2 and,together with hydrophobic payloads at high DARs(drug-toantibody ratios),may turn ADC molecules that have hydrophilic parts in their antibody portions,into aggregation-prone“surfactant-like”structures.
