91575-51-8Relevant academic research and scientific papers
Site-specific tagging proteins with a rigid, small and stable transition metal chelator, 8-hydroxyquinoline, for paramagnetic NMR analysis
Yang, Yin,Huang, Feng,Huber, Thomas,Su, Xun-Cheng
, p. 103 - 113 (2016/02/23)
Design of a paramagnetic metal binding motif in a protein is a valuable way for understanding the function, dynamics and interactions of a protein by paramagnetic NMR spectroscopy. Several strategies have been proposed to site-specifically tag proteins with paramagnetic lanthanide ions. Here we report a simple approach of engineering a transition metal binding motif via site-specific labelling of a protein with 2-vinyl-8-hydroxyquinoline (2V-8HQ). The protein-2V-8HQ adduct forms a stable complex with transition metal ions, Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). The paramagnetic effects generated by these transition metal ions were evaluated by NMR spectroscopy. We show that 2V-8HQ is a rigid and stable transition metal binding tag. The coordination of the metal ion can be assisted by protein sidechains. More importantly, tunable paramagnetic tensors are simply obtained in an α-helix that possesses solvent exposed residues in positions i and i + 3, where i is the residue to be mutated to cysteine, i + 3 is Gln or Glu or i - 4 is His. The coordination of a sidechain carboxylate/amide or imidazole to cobalt(II) results in different structural geometries, leading to different paramagnetic tensors as shown by experimental data.
Synthesis and biological properties of Quilamines II, new iron chelators with antiproliferative activities
Corcé, Vincent,Renaud, Stéphanie,Cannie, Isabelle,Julienne, Karine,Gouin, Sébastien G.,Loréal, Olivier,Gaboriau, Fran?ois,Deniaud, David
, p. 320 - 334 (2014/03/21)
To selectively target tumor cells expressing an overactive Polyamine Transport System (PTS), we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, derived from the lead compound HQ1-44, which we named Quilamines II. The structures of four new antiproliferative agents were developed. They differ in the size of the linker (HQ0-44 and HQ2-44) or in the nature of the linker (HQCO-44 and HQCS-44) between a hydroxyquinoline moiety (HQ) and a homospermidine (44) chain, the best polyamine vector. The Quilamines II were obtained after 6 to 9 steps by Michael addition, peptide linkage, and reductive amination or by using the Willgerodt-Kindler reaction. The biological evaluation of these second-generation Quilamines showed that modifying the size of the linker increased the selectivity of these compounds for the PTS. In addition, measurement of the toxicity of Quilamines HQ0-44 and HQ2-44 highlighted their marked antiproliferative nature on several cancerous cell lines as well as a differential activity on nontransformed cells (fibroblasts). In contrast, Quilamines HQCO-44 and HQCS-44 presented low selectivity for the PTS, probably due to a loss of electrostatic interaction. We also demonstrated that the HCT116 cell line, originating from a human colon adenocarcinoma, was the most responsive to the various Quilamines. As deduced from the calcein and HVA assays, the higher iron chelating capacity of HQ1-44 could explain its higher antiproliferative efficiency.
SYNTHESIS OF 2-VINYL-8-QUINOLINOL AND MEASUREMENT OF STABILITY OF ITS METAL COMPLEXES
Yoneda, Akio,Azumi, Takatsugu
, p. 1191 - 1194 (2007/10/02)
2-Vinyl-8-quinolinol was prepared in 30 percent yield from 2-formyl-8-quinolinol by Wittig reaction.The acid dissociation constants of 2-vinyl-8-quinolinol and the stability constants of the chelates of the reagent with some divalent metals have been determined by titration techniques.The chelates are less stable than those of 8-quinolinol and 2-methyl-8-quinolinol.
