Investigation of 1-Methylcytosine as a Ligand in Gold(III) Complexes: Synthesis and Protein Interactions

Autor: Nicholas Farrell, James Beaton
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Inorganics
Volume 7
Issue 1
Inorganics, Vol 7, Iss 1, p 1 (2018)
ISSN: 2304-6740
DOI: 10.3390/inorganics7010001
Popis: The HIV nucleocapsid protein NCp7 was previously shown to play a number of roles in the viral life cycle and was previously identified as a potential target for small molecule intervention. In this work, the synthesis of the previously unreported complexes [Au(dien)(1MeCyt)]3+, [Au(N-Medien)(1MeCyt)]3+, and [Au(dien)(Cyt)]3+ is detailed, and the interactions of these complexes with the models for NCp7 are described. The affinity for these complexes with the target interaction site, the &ldquo
essential&rdquo
tryptophan of the C-terminal zinc finger motif of NCp7, was investigated through the use of a fluorescence quenching assay and by 1H-NMR spectroscopy. The association of [Au(dien)(1MeCyt)]3+ as determined through fluorescence quenching is intermediate between the previously reported DMAP and 9-EtGua analogs, while the associations of [Au(N-Medien)(1MeCyt)]3+ and [Au(dien)(Cyt)]3+ are lower than the previously reported complexes. Additionally, NMR investigation shows that the self-association of relevant compounds is negligible. The specifics of the interaction with the C-terminal zinc finger were investigated by circular dichroism spectroscopy and electrospray-ionization mass spectrometry. The interaction is complete nearly immediately upon mixing, and the formation of AuxFn+ (x = 1, 2, or 4
F = apopeptide) concomitant with the loss of all ligands is observed. Additionally, oxidized dimerized peptide was observed for the first time as a product, indicating a reaction via a charge transfer mechanism.
Databáze: OpenAIRE
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