Human Serum Albumin-Delivered [Au(PEt)] 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] ( = phosphine ligand; = 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(PEt)] and [Au(JohnPhos)] (JohnPhos = 1,1'-biphenyl-2-yl)di--butylphosphine) in compounds and were transferred to recombinant human serum albumin (rHSA). PEt promoted efficient modification of Cys34 in HSA (), whereas use of bulky JohnPhos as a carrier ligand led to serum protein nonspecifically modified with multiple gold adducts () (Ellman's test, ESI-TOF MS). , but not , 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.