Although recent methods for the engineering of antibody-drug conjugates (ADCs) have gone some way to addressing the challenging issues of ADC construction, significant hurdles still remain. There is clear demand for the construction of novel ADC platforms that offer greater stability, homogeneity and flexibility. Here we describe a significant step towards… (More)
General Experimental All reagents were purchased from Sigma-Aldrich or AlfaAesar and were used as received without further purification. Where described below petrol refers to petrol (b.p. 40-60 °C). All reactions were monitored by thin-layer chromatography (TLC) on pre-coated SIL G/UV254 silica gel plates (254 m) purchased from VWR. Flash column… (More)
It has recently emerged that the succinimide linkage of a maleimide thiol addition product is fragile, which is a major issue in fields where thiol functionalisation needs to be robust. Herein we deliver a strategy that generates selective cysteine thiol labelling reagents, which are stable to hydrolysis and thiol exchange.
Herein we present a significant step towards next-generation antibody-based photodynamic therapeutics. Site-selective modification of a clinically relevant monoclonal antibody, with a serum-stable linker bearing a strained alkyne, allows for the controlled Cu-free "click" assembly of an in vitro active antibody-based PDT agent using a water soluble azide… (More)
Bromomaleimides are useful building blocks in synthesis and powerful reagents for the selective chemical modification of proteins. A mild new synthesis of these reagents is described, along with the convenient transferability of the approach to dithiomaleimides and bromopyridazinediones.
Please do not adjust margins Please do not adjust margins a. a Recent advances in nanomedicine have shown that dramatic improvements in nanoparticle therapeutics and diagnostics can be achieved through the use of disease specific targeting ligands. Although immunoglobulins have successfully been employed for the generation of actively targeted… (More)
DARPin genes were purchased from Genscript in the vector pUC57, flanked by the upstream and downstream T7 control sequences used in pET21. Sequences of purchased genes are provided in Supplementary Data 1. The primers used are provided in Supplementary Table 1, and all mutations were confirmed by DNA sequencing. DARPins were expressed directly from pUC57… (More)