The zinc finger protein tristetraprolin (TTP) regulates inflammation by downregulatingc ytokinem RNAs. Misregulation resultsi na rthritis, sepsis and cancer,a nd there is an interesti nm odulating TTP activity with exogenous agents. Gold hasa nti-inflammatory properties and has recently been shown to modulate the signaling pathway that produces TTP,s uggesting that TTP may be at arget of gold. The reactivity of [Au III (terpy)Cl]Cl 2 with TTPw as investigated by UV/Vis spectroscopy,s pin-filter inductively coupled plasma mass spectrometry,X -ray absorption spectroscopy and native electrospray ionization mass spectrometry.A u III was found to replace zinc in the protein active site in the reduced Au I form, with the Au I ion coordinated to two cysteine residues in al inear geometry.T he replacement of Zn II with Au I resultsi nl oss of both secondary structure and RNA binding function. In contrast, when Zn II TTP is boundt oi ts RNA target, no replacement of Zn II with Au I is observed, even in the presence of excessA u III terpy.T his discovery of differential reactivity of gold with TTP versus TTP/RNA offers ap otentials trategy for selectivet argeting with gold complexest oc ontroli nflammation.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.org/10.1002/chem.201904837.Scheme1.Cartoon diagram of role of TTP in TNF-a signaling. TTP (in yellow) regulates TNF-a by binding to and degrading its mRNA as part of the NF-kBs ignaling pathway.

Native nano ESI‐mass spectrometry can be applied to track the formation of “Gold Fingers” formed when AuIII‐terpy reacts with the non‐classical zinc finger protein tristetraprolin. This powerful MS technique can also be utilized to probe reactivity of RNA bound zinc fingers, and it is reported that RNA has a protective effect towards Gold Finger reactivity with tristetraprolin. For more details, see the Full Paper by S. L. J. Michel and co‐workers on page 1535 ff.