The reaction of dichlorodiammineplatinum(II), [PtCl2(NH3)2], isomers with zinc fingers

Guo

et al. 2021

Viruses

The nucleocapsid (NC) protein of human immunodeficiency (HIV) is a small, highly basic protein containing two CCHC zinc-finger motifs, which is cleaved from the NC domain of the Gag polyprotein during virus maturation. We previously reported that recombinant HIV-1 Gag and NCp7 overexpressed in an E. coli host contains two and one zinc ions, respectively, and Gag exhibited much higher selectivity for packaging signal (Psi) and affinity for the stem-loop (SL)-3 of Psi than NCp7. In this study, we prepared NCp7 containing 0 (0NCp7), 1 (NCp7) or 2 (2NCp7) zinc ions, and compared their secondary structure, Psi-selectivity and SL3-affinity. Along with the decrease of the zinc content, less ordered conformations were detected. Compared to NCp7, 2NCp7 exhibited a much higher Psi-selectivity and SL3-affinity, similar to Gag, whereas 0NCp7 exhibited a lower Psi-selectivity and SL3-affinity, similar to the H23&H44K double mutant of NCp7, indicating that the different RNA-binding property of Gag NC domain and the mature NCp7 may be resulted, at least partially, from their different zinc content. This study will be helpful to elucidate the critical roles that zinc played in the viral life cycle, and benefit further investigations of the functional switch from the NC domain of Gag to the mature NCp7.

Section: Comparison Of the Conformation Of 0 Ncp7 Ncp7 And 2 Ncp7supporting

confidence: 75%

The Zinc Content of HIV-1 NCp7 Affects Its Selectivity for Packaging Signal and Affinity for Stem-Loop 3

Guo

et al. 2021

Viruses

“…Since the American scientist B. Rosenborg serendipitously found that cisplatin possessed a strong anticancer activity, metal‐based drugs have attracted widespread attention of medical scientists. As one of the earliest drugs to be used in the treatment of tumors, cisplatin is one of the most commonly used in combination chemotherapy, while its high toxicity and side effects also brought a lot of pain to patients . Inspired by this, many chemists have paid attention to the development of new metal‐based drugs in order to overcome the drawbacks of cisplatin .…”

Section: Introductionmentioning

confidence: 99%

Two Ho(III) and Co(II) complexes constructed from bis(triazol‐1‐yl)benzoic acid with structurally similar carboxyl ligands: Syntheses, structures and biological activities

Zhu

Meng

et al. 2018

Applied Organom Chemis

Two new complexes, [Ho(L) 2 NO 3 ] n (1) and [Co(L′) 2 Cl 4 ] n (2) (HL = 3,5bis(triazol-1-yl)benzoic acid, HL′ = 2,4-bis(triazol-1-yl)benzoic acid), have been synthesized and characterized. Interactions with DNA through absorption titration experiments, fluorescence spectra, viscosity measurements and a molecular docking study were examined. The results suggested that complexes 1 and 2 interact with DNA in a partial intercalation mode. DNA binding affinity was determined using k b values, which indicated that the binding activity of the complexes to DNA was complex 2 (k b = 1.93 × 10 4 ) > complex 1 (k b = 1.06 × 10 4 ). Gel electrophoresis assay demonstrated that the complexes have the ability to cleave pBR322 DNA. Apoptotic assay indicated that the complexes can induce programmed death of Hela cells (human cervix carcinoma cells). A cytotoxicity study indicated that complex 2 shows a greater inhibitory rate of Hela cells than complex 1 and the cytotoxicity of both 1 and 2 showed time dependence. Especially, the efficacy of complex 2 was shown to be higher than that of cisplatin at 72 h.

“…The recognition of the importance of coordination isomers has opened a new era in metallopharmaceutical design. 45,46 Drug delivery, 47 bioprocessing, [48][49][50] drug activity, [51][52][53] drug selectivity 26,54 and resistance [55][56][57][58][59] can be optimized by selecting an isomeric drug or a prodrug with the best properties.…”

Section: Introductionmentioning

confidence: 99%

Exploring the boundaries of direct detection and characterization of labile isomers – a case study of copper(ii)–dipeptide systems

et al. 2017

The investigation of the linkage isomers of biologically essential and kinetically labile metal complexes in aqueous solutions poses a challenge, as these microspecies cannot be separately studied. Therefore, derivatives are commonly used to initially determine the stability or spectral characteristics of at least one of the isomers. Here we directly detect the isomers, describe the metal ion coordination sphere, speciation and thermodynamic parameters by a synergistic application of temperature dependent EPR and CD spectroscopic measurements in copper(ii)-dipeptide systems including His-Gly and His-Ala ligands. The ΔH = (-23 ± 4) kJ mol value of the standard enthalpy change corresponding to the peptide-type to histamine-type isomerisation equilibrium of the [CuL] complex was corroborated by several techniques. The preferential coordination of the side-chains was observed at lower temperatures, whereas, metal-binding of the backbone atoms became favourable upon increasing temperature. This study exemplifies the necessity of using temperature dependent multiple methodologies for a reliable description of similar systems for upstream applications.