SLF TFA is a synthetic ligand for FK506-binding protein (FKBP) with an affinity of 3.1 μM for FKBP51 and an IC50 of 2.6 μM for FKBP12. SLF TFA can be used in the synthesis of PROTAC[1][2][3].
Three scout fragments-KB02, KB03, and KB05 are fused, which cover two different electrophile groups (chloroacetamide and acrylamide) and display broad cysteine reactivity in the human proteome-to the SLF ligand that binds tightly and selectively to FKBP12, a cytosolic prolyl isomerase that has been frequently used to study ligand-induced protein degradation[3].
[1]. Kolos JM, et al. FKBP Ligands-Where We Are and Where to Go• Front Pharmacol. 2018 Dec 5;9:1425. [2]. Wu X, et al. Creating diverse target-binding surfaces on FKBP12: synthesis and evaluation of a rapamycin analogue library. ACS Comb Sci. 2011 Sep 12;13(5):486-95. [3]. Zhang X, et al. Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16. Nat Chem Biol. 2019 Jul;15(7):737-746.