WL47 is a high-affinity ligand for caveolin-1 (CAV1) with a dissociation constant (Kd) of 23 nM, demonstrating potent disruption of CAV1 oligomers. This compound exhibits selectivity for CAV1, with minimal interaction towards BSA, casein, and HEWL. Notably, WL47's molecular structure is 80% smaller than its T20 parent sequence, rendering it a useful tool for investigating caveolin-1 function [1].

Caveolin-1 (CAV) is a 22 kDa monotopic membrane protein that spans a single leaflet of the lipid bilayer with both the N- and C-termini facing the cytoplasmic side. CAV oligomerization results in the formation of high molecular weight complexes, which induce membrane curvature to generate 50-100 nm invaginations known as 'caveolae.'

The peptide T20, a 36 amino acid fragment derived from HIV gp41, inhibits viral fusion with CD4+ T-cells. WL47, which is 80% shorter, exhibits a 7500-fold higher affinity than its T20 progenitor. In vitro studies reveal WL47’s interaction with CAV oligomers and contribute a methodology to quantify oligomerization. Using a CAV variant (CAV(FLV)) that forms spontaneous CAV nanoparticles, WL47 is shown to effectively deoligomerize these structures. However, WL47's ability to disrupt oligomerization is contingent on the absence of a reducing agent, indicating a disulfide bond-mediated dimerization is essential for its activity.