Proton NMR spectroscopy and cyclic voltammetry have been applied to study the stability of three gold(III) complexes with L-histidine-containing peptides, [Au(Gly-L-His-N,N’,N’’)Cl]NO3.1.25H2O (Au1), [Au(L-Ala-L-His-N,N’,N’’)Cl]NO3.2.5H2O (Au2) and [Au(Gly-Gly-L-His-N,N’,N’’,N’’’)]Cl.H2O (Au3) under physiologically relevant conditions. It was found that tridentate coordination of Gly-L-His and L-Ala-L-His dipeptides, as well as tetradentate coordination of Gly-Gly-L-His tripeptide in Au1, Au2 and Au3 complexes, respectively, stabilized +3 oxidation state of gold and prevented its reduction to Au(I) and Au(0). No release of the coordinated peptides from Au(III) was observed under these experimental conditions. Considering remarkable stability of Au1, Au2 and Au3 complexes, their cytotoxic activity was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay toward five human tumor cell lines, MCF-7 (human breast adenocarcinoma), HT-29 (human colon adenocarcinoma), HeLa (human cervix carcinoma), HL-60 (human promyelocytic leukemia), Raji (human Burkitt’s lymphoma) and one human normal cell line MRC-5 (human fetal lung fibroblasts). While the cytotoxic activity of Au1, Au2 and Au3 against investigated human malignant cell lines was strongly cell line dependent, none of these complexes was cytotoxic against normal MRC-5 cell line. This study can contribute to the future development of gold(III)-peptide complexes as potential antitumor agents.

Background: Neonatal dried blood spots (Guthrie cards) have been used to demonstrate a prenatal origin of clonal leukemia-specific genetic aberrations in several subgroups of childhood acute lymphoblastic leukemia (ALL). One hypothesis suggests that an infectious agent could initiate genetic transformation already in utero. In search for a possible viral agent, Guthrie cards were analyzed for the presence of 3 newly discovered polyomavirus Karolinska Institutet polymavirus (KIPyV), Washington University polyomavirus (WUPyV), and Merkel cell polyomavirus (MCPyV). Methods: Guthrie cards from 50 children who later developed ALL and 100 matched controls were collected and analyzed by standard or real-time polymerase chain reaction for the presence of the VP1 region of KIPyV, WUPyV, and MCPyV, and the LT region for MCPyV. Results and Conclusions: DNA from KIPyV, WUPyV, and MCPyV was not detected in neonatal blood samples from children with ALL or controls. Prenatal infections with these viruses are not likely to be etiological drivers for childhood leukemogenesis.