Formation of mono- and dual-labelled antibody fragment conjugates reversible site-selective disulfide modification and proximity induced lysine reactivity.

Many protein bioconjugation strategies focus on the modification of lysine residues owing to the nucleophilicity of their amine side-chain, the generally high abundance of lysine residues on a protein's surface and the ability to form robustly stable amide-based bioconjugates. However, the plethora of solvent accessible lysine residues, which often have similar reactivity, is a key inherent issue when searching for regioselectivity and/or controlled loading of an entity. A relevant example is the modification of antibodies and/or antibody fragments, whose conjugates offer potential for a wide variety of applications.

Enabling the formation of native mAb, Fab' and Fc-conjugates using a bis-disulfide bridging reagent to achieve tunable payload-to-antibody ratios (PARs).

Either as full IgGs or as fragments (Fabs, Fc, ), antibodies have received tremendous attention in the development of new therapeutics such as antibody-drug conjugates (ADCs). The production of ADCs involves the grafting of active payloads onto an antibody, which is generally enabled by the site-selective modification of native or engineered antibodies chemical or enzymatic methods. Whatever method is employed, controlling the payload-antibody ratio (PAR) is a challenge in terms of multiple aspects including: (i) obtaining homogeneous protein conjugates; (ii) obtaining unusual PARs (PAR is rarely other than 2, 4 or 8); (iii) using a single method to access a range of different PARs; (iv) applicability to various antibody formats; and (v) flexibility for the production of heterofunctional antibody-conjugates ( attachment of multiple types of payloads).

Functionalisation of ethereal-based saturated heterocycles with concomitant aerobic C-H activation and C-C bond formation.

With an ever-growing emphasis on sustainable synthesis, aerobic C-H activation (the use of oxygen in air to activate C-H bonds) represents a highly attractive conduit for the development of novel synthetic methodologies. Herein, we report the air mediated functionalisation of various saturated heterocycles and ethers aerobically generated radical intermediates to form new C-C bonds using acetylenic and vinyl triflones as radical acceptors. This enables access to a variety of acetylenic and vinyl substituted saturated heterocycles that are rich in synthetic value.