Work

Human Serum Albumin-Delivered [Au(PEt3)]+ Is a Potent Inhibitor of T Cell Proliferation

Year: 2017

Type: article

Abstract: 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(PEt 3 )] + 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). PEt 3 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.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.7b00142