PROteolysis TArgeting Chimeras (PROTACs) have emerged as an exciting new modality in drug discovery for catalytically inducing targeted protein degradation. They consist of protein binding ligands for an E3 ubiquitin ligase and the protein to be degraded joined together by a linker, the length and composition of which can greatly affect the biological activity and physical properties of the PROTACs. Fluorination is an oft-used strategy in medicinal chemistry for modulation of properties like lipophilicity and membrane permeability, as well as conformational control, and we envisioned incorporation of fluorine into the linker as a means to potentially modulate these properties of the degrader. The synthesis of PROTACs with fluorinated linkers, and the characterisation of their activity and physicochemical properties is reported here.Using a pentanediol scaffold (to enable functionalisation at either end for PROTAC incorporation), a series of compounds with a “skipped” fluorination pattern were initially synthesised. Their lipophilicity was measured using a 19F NMR technique developed within the Linclau group, through which the lipophilicity-reducing potential of these motifs was demonstrated. Subsequently, these skipped fluorinated motifs were incorporated as novel linker designs for PROTACs. These compounds were characterised using an array of biological and DMPK assays, with a view to investigate the effects that these fluorination patterns may have on the potency, selectivity, and physical properties of our PROTACs.