WL47 TFA, a high-affinity cavolin-1 (CAV1) ligand (Kd=23 nM), potently disrupts CAV1 oligomers and exhibits selectivity over BSA, casein, and HEWL. At 80% shorter than the original T20 parent sequence, WL47 TFA is used to investigate caveolin-1 function [1].

Caveolin-1 (CAV), a 22 kDa integral membrane protein, selectively inserts into one leaflet of the lipid bilayer, with both the N- and C-termini facing the cytoplasm. It oligomerizes into high molecular weight complexes, inducing the membrane to form 'caveolae' invaginations, 50-100 nm in diameter. The peptide T20, derived from HIV's gp41, inhibits HIV fusion with CD4+ T-cells, whereas the much smaller WL47, with a 7500-fold higher affinity, outperforms T20. In vitro experiments demonstrate WL47's interaction with CAV oligomers and provide a method to quantify oligomerization. Using a CAV variant (CAV(FLV)), which forms nanoparticles through spontaneous oligomerization, WL47 is shown to effectively dismantle these structures. Notably, WL47 does not interfere with oligomerization in the presence of a reducing agent, indicating that its activity relies on stabilizing disulfide bond-mediated dimerization.