TY - JOUR
T1 - Induction of the 32-kD human stress protein by auranofin and related triethylphosphine gold analogs
AU - Caltabiano, Madelyn M.
AU - Poste, George
AU - Greig, Russell G.
PY - 1988/11/1
Y1 - 1988/11/1
N2 - Challenge of human cells with auranofin, 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranosato-S-triethylphosphine gold(I) (Ridaura), a gold-containing compound approved by the FDA for the treatment of rheumatoid arthritis, induces the specific synthesis of a 32-kD stress protein (p32) [Caltabiano et al., Biochem. biophys. Res. Commun. 138, 1074 (1986)]. To establish a structure-activity relationship for this effect, a series of auranofin ligands, gold analogs, and other anti-arthritic agents were examined for their abilities to stimulate p32 synthesis. The results indicate that the gold atom is necessary for enhanced expression of p32. However, the structure of co-ordinated ligands also affected potency, and gold complexes bearing several phosphine or thiosugar groups exhibited the greatest activity. These data indicate that the distinct potencies of auranofin analogs probably reflect their membrane permeability and subsequent delivery of pharmacologically active concentrations of gold to the cytoplasmic compartment.
AB - Challenge of human cells with auranofin, 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranosato-S-triethylphosphine gold(I) (Ridaura), a gold-containing compound approved by the FDA for the treatment of rheumatoid arthritis, induces the specific synthesis of a 32-kD stress protein (p32) [Caltabiano et al., Biochem. biophys. Res. Commun. 138, 1074 (1986)]. To establish a structure-activity relationship for this effect, a series of auranofin ligands, gold analogs, and other anti-arthritic agents were examined for their abilities to stimulate p32 synthesis. The results indicate that the gold atom is necessary for enhanced expression of p32. However, the structure of co-ordinated ligands also affected potency, and gold complexes bearing several phosphine or thiosugar groups exhibited the greatest activity. These data indicate that the distinct potencies of auranofin analogs probably reflect their membrane permeability and subsequent delivery of pharmacologically active concentrations of gold to the cytoplasmic compartment.
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U2 - 10.1016/0006-2952(88)90100-1
DO - 10.1016/0006-2952(88)90100-1
M3 - Article
C2 - 3190747
AN - SCOPUS:0023757431
SN - 0006-2952
VL - 37
SP - 4089
EP - 4093
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 21
ER -