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

ACS Medicinal Chemistry Letters
Tyler C DeanUlrich Bierbach

Abstract

Using a modular library format in conjunction with cell viability (MTS) and flow cytometry assays, 90 cationic complexes [AuPL] (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.

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Citations

Mar 7, 2018·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Benelita T ElieMaría Contel
Apr 20, 2020·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Sophia Sarpong-KumankomahJürgen Gailer
May 18, 2021·Journal of Medicinal Chemistry·Juzheng ZhangHong Liang

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