Human Serum Albumin-Delivered [Au(PEt 3 )] + Is a Potent Inhibitor of T Cell Proliferation.

Using a modular library format in conjunction with cell viability (MTS) and flow cytometry assays, 90 cationic complexes [Au PL ] n + ( P = phosphine ligand; L = thiourea derivative or chloride) were studied for their antiproliferative activity in CD8+ T lymphocyte cells. The activity of the compounds correlates with the steric bulk of the phosphine ligands. Thiourea serves as a leaving group that is readily replaced by cysteine thiol (NMR, ESI-MS). Taking advantage of selective thiourea ligand exchange, the fragments [Au(PEt3 )]+ and [Au(JohnPhos)]+ (JohnPhos = 1,1'-biphenyl-2-yl)di- tert -butylphosphine) in compounds 1 and 2 were transferred to recombinant human serum albumin (rHSA). PEt3 promoted efficient modification of Cys34 in HSA ( HSA-1 ), whereas use of bulky JohnPhos as a carrier ligand led to serum protein nonspecifically modified with multiple gold adducts ( HSA-2 ) (Ellman's test, ESI-TOF MS). HSA-1 , but not HSA-2 , strongly inhibits T cell proliferation at nanomolar doses. The potential role of HSA as a delivery vehicle in gold-based autoimmune disease treatment is discussed.