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MICROCHIMICA ACTA · 2021 ·Vol. 188 ·期 6 ·1-8 · IF 5.833

l-Histidine-DNA interaction: a strategy for the improvement of the fluorescence signal of poly(adenine) DNA-templated gold nanoclusters

Wang Hai-Bo,Mao An-Li,Tao Bei-Bei,Zhang Hong-Ding,Xiao Zhong-Liang,Liu Yan-Ming

An interesting phenomenon is described that the fluorescence signal of poly(adenine) (A) DNA-templated gold nanoclusters (AuNCs) is greatly improved in the presence of l -histidine by means of l -histidine-DNA interaction. The modified nanoclusters display strong fluorescence emission with excitation/emission maxima at 290/475 nm. The fluorescence quantum yield (QY) is improved from 1.9 to 6.5%. Fluorescence enhancement is mainly ascribed to the l -histidine-DNA interaction leading to conformational changes of the poly(A) DNA template, which offer a better microenvironment to protect AuNCs. The assay enables l -histidine to be determined with good sensitivity and a linear response that covers the 1 to 50 nM  l -histidine concentration range with a 0.3 nM limit of detection. The proposed method has been applied to the determination of imidazole-containing drugs in pharmaceutical samples. Graphical abstract A turn-on fluorescent method has been designed for the sensitive detection of l -histidine as well as imidazole-containing drugs on the basis of the l -histidine-DNA interaction.

CAS / MDL: 16961-25-4 68-04-2
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Materials · 2021 ·Vol. 14 ·期 16 ·4674 · IF 3.623

Development and Characterization of High Efficacy Cell-Penetrating Peptide via Modulation of the Histidine and Arginine Ratio for Gene Therapy

Yu Liu,Huan-Huan Wan,Duo-Mei Tian,Xiao-Jun Xu,Chang-Long Bi,Xiao-Yong Zhan,Bi-Hui Huang,Yun-Sheng Xu,Le-Ping Yan

Cell-penetrating peptides (CPPs), as non-viral gene delivery vectors, are considered with lower immunogenic response, and safer and higher gene capacity than viral systems. In our previous study, a CPP peptide called RALA (arginine rich) presented desirable transfection efficacy and owns a potential clinic use. It is believed that histidine could enhance the endosome escaping ability of CPPs, yet RALA peptide contains only one histidine in each chain. In order to develop novel superior CPPs, by using RALA as a model, we designed a series of peptides named HALA (increased histidine ratio). Both plasmid DNA (pDNA) and siRNA transfection results on three cell lines revealed that the transfection efficacy is better when histidine replacements were on the C-terminal instead of on the N-terminal, and two histidine replacements are superior to three. By investigating the mechanism of endocytosis of the pDNA nanocomplexes, we discovered that there were multiple pathways that led to the process and caveolae played the main role. During the screening, we discovered a novel peptide-HALA2 of high cellular transfection efficacy, which may act as an exciting gene delivery vector for gene therapy. Our findings also bring new insights on the development of novel robust CPPs.Keywords:gene therapy;cell penetrating peptide;histidine;RALA peptide;endosomal escaping

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RSC Advances · 2020 ·Vol. 10 ·期 19 ·11524-11534 · IF 3.119

Synthesis of magnetic nanoparticles with an IDA or TED modified surface for purification and immobilization of poly-histidine tagged proteins

Kai Zeng,En-Jie Sun,Ze-Wen Liu,Junhui Guo,Chengqing Yuan,Ying Yang,Hao Xie

Magnetic nanoparticles (MNPs) chelating with metal ions can specifically interact with poly-histidine peptides and facilitate immobilization and purification of proteins with poly-histidine tags. Fabrication of MNPs is generally complicated and time consuming. In this paper, we report the preparation of Ni(II) ion chelated MNPs (Ni-MNPs) in two stages for protein immobilization and purification. In the first stage, organic ligands including pentadentate tris (carboxymethyl) ethylenediamine (TED) and tridentate iminodiacetic acid (IDA) and inorganic Fe3O4–SiO2 MNPs were synthesized separately. In the next stage, ligands were grafted to the surface of MNPs and MNPs with a TED or IDA modified surface were acquired, followed by chelating with Ni(II) ions. The Ni(II) ion chelated forms of MNPs (Ni-MNPs) were characterized including morphology, surface charge, structure, size distribution and magnetic response. Taking a his-tagged glycoside hydrolase DspB (Dispersin B) as the protein representative, specific interactions were confirmed between DspB and Ni-MNPs. Purification of his-tagged DspB was achieved with Ni-MNPs that exhibited better performance in terms of purity and activity of DspB than commercial Ni-NTA. Ni-MNPs as enzyme carriers for DspB also exhibited good compatibility and reasonable reusability as well as improved performance in various conditions.

CAS / MDL: 919-30-2 1760-24-3
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MICROCHIMICA ACTA · 2020 ·Vol. 187 ·期 1 ·1-7 · IF 6.232

Fluorimetric determination of histidine by exploiting its inhibitory effect on the oxidation of thiamine by cobalt-containing Prussian Blue nanocubes

Yao Zhixia,Liu Hanmeng,Liu Yaosheng,Zhang Qifang,Diao Yongxing,Sun Yujing,Li Zhuang

A fluorometric assay for histidine (His) is described. It is based on the inhibitory effect of His on nanocubes consisting of cobalt-containing Prussian Blue analog (CoFe NCbs), which have a strong oxidation effect on thiamine (THI) in the presence of NaOH. THI is nonfluorescent but the oxidized form (thiochrome; ThC) has a strong blue fluorescence, with excitation/emission maxima at 370/445 nm. His inhibits the oxidation effect of the CoFe NCbs due to the strong interaction between its imidazole side chain and the amino groups of the CoFe NCbs. This method is fast and has good sensitivity and selectivity. The lower detection limit is 14.3 nM of His, the linear range extends from 0.05 to 2.5 μM, and the relative standard deviation is calculated to be 1.5%. The method was successfully employed to quantify His in spiked serum samples. Schematic representation of cobalt-containing Prussian Blue nanocubes (CoFe NCbs)-thiamine (THI)-based fluorometric assay for Histine (His). His inhibits the generation of thiochrome (ThC; the oxidized form of THI). The detection limit is 14.3 nM with the linear range of 0.05–2.5 μM.

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ANALYTICAL CHEMISTRY · 2018 · IF 6.042

Self-Assembled Binuclear Cu(II)–Histidine Complex for Absolute Configuration and Enantiomeric Excess Determination of Naproxen by Tandem Mass Spectrometry

Xiangying Yu,Man-Chu Chau,Wai Kit Tang,Chi-Kit Siu,Zhong-Ping Yao

Naproxen is one of the most consumed nonsteroidal anti-inflammatory drugs and marketed as S-naproxen since R-naproxen is hepatotoxic. In this study, chiral recognition of naproxen has been investigated by tandem mass spectrometry (MS/MS). Among all diastereomeric complexes formed between naproxen and the examined chiral selectors, including cyclodextrins (α/β/γ-CD), modified phenylalanines (N-acetyl-phenylalanine, N-t-butoxycarbonyl-phenylalanine, N-9-fluorenylmethyloxycarbonyl-phenylalanine), amino acids (Trp, Phe, Tyr, His), glucose, tartaric acid, and vancomycin, a novel binuclear metal bound diastereomeric complexes [(M(II))2(S/R-naproxen)(l-His)2−3H]+ (M = Cu, Ni, or Co with Cu being the best) could allow effective identification of the absolute configuration of naproxen and determination of its enantiomeric excess (ee) through MS/MS analysis. The key candidate structure of [(Cu(II))2(S/R-naproxen)(l-His)2−3H]+ has been revealed by means of collision-induced dissociation, ion mobility mass spectrometry and density functional theory calculations, indicating an interesting and unusual self-assembled compact geometry with the two Cu(II) ions bridged closely together (Cu–Cu distance is 3.04 Å) by the carboxylate groups of the two histidines. It was shown that the difference in dissociation efficiency between the two diastereomers was attributed to the interaction between the NH2 bond of the amino group of one histidine and the naphthyl ring of naproxen. The present report is the first to observe and characterize the complex of (Cu(II))2(His)2 with aromatic acid, which could contribute to the chiral recognition of other chiral aromatic acids, design of catalysts based on binuclear copper bound complex, as well as the better understanding of metal ion complexation by His or His-containing ligands.

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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Integrated Logic Gate for Fluorescence Turn-on Detection of Histidine and Cysteine Based on Ag/Au Bimetallic Nanoclusters–Cu2+ Ensemble

Jian Sun,Fan Yang,Dan Zhao,Chuanxia Chen,Xiurong Yang

By means of employing 11-mercaptoundecanoic acid (11-MUA) as a reducing agent and protecting ligand, we present straightforward one-pot preparation of fluorescent Ag/Au bimetallic nanoclusters (namely AgAuNCs@11-MUA) from AgNO3 and HAuCl4 in alkaline aqueous solution at room temperature. It is found that the fluorescence of AgAuNCs@11-MUA has been selectively quenched by Cu2+ ions, and the nonfluorescence off-state of the as-prepared AgAuNCs@11-MUA–Cu2+ ensemble can be effectively switched on upon the addition of histidine and cysteine. By incorporating Ni2+ ions and N-ethylmaleimide, this phenomenon is further exploited as an integrated logic gate and a specific fluorescence turn-on assay for selectively and sensitively sensing histidine and cysteine has been designed and established based on the original noncovalent AgAuNCs@11-MUA–Cu2+ ensemble. Under the optimal conditions, histidine and cysteine can be detected in the concentration ranges of 0.25–9 and 0.25–7 μM; besides, the detection limits are found to be 87 and 111 nM (S/N = 3), respectively. Furthermore, we demonstrate that the proposed AgAuNCs@11-MUA-based fluorescent assay can be successfully utilized for biological fluids sample analysis.

CAS / MDL: 7365-45-9 1310-73-2
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SPECTROSCOPY LETTERS · 2015 · IF 0.852

Novel Glutathione-Capped Cadmium Telluride Quantum Dots-Based Off–On Fluorescence Sensor for Highly Sensitive and Selective Monitoring of Histidine

Jidong Yang,Shaopu Liu,Linlin Wang,Chenxia Hao,Huiping Gong,Yizhong Shen,Youqiu He

A novel glutathione-capped cadmium telluride quantum dots-based fluorescence “off–on” sensor was designed and applied for highly sensitive and selective monitoring of histidine in aqueous solution. To provide a platform for histidine detection, manganese ion was first employed as an effective quencher to decrease the fluorescence of glutathione-capped cadmium telluride quantum dots because of the binding of manganese ion to glutathione on the surface of quantum dots and the electron transfer from the photoexcited glutathione-capped cadmium telluride quantum dots to manganese ion. Due to its high binding affinity with manganese ion, histidine can make the manganese ion to be dissociated from the surface of glutathione-capped cadmium telluride quantum dots to form more stable complex with histidine in solution, and set free the luminescent glutathione-capped cadmium telluride quantum dots, thereby recovering the fluorescence of glutathione-capped cadmium telluride quantum dots. Experimental results showed that the recovered fluorescence intensity was directly proportional to the concentration of histidine in the range of 0.006 to 465.0 µg mL−1 with a correlation coefficient (R) of 0.9977, and the detection limit (3σ/K) was 1.82 ng mL−1. Relevant experiments also revealed that the fluorescence sensor gives excellent selectivity for histidine over other common amino acids. To further investigate perfect analysis performance, this sensor was utilized to determine histidine in synthetic samples with satisfactory results.

CAS / MDL: 70-18-8 71-00-1
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2017 · IF 2.536

Highly sensitive “turn-on” fluorescent chemical sensor for trace analysis of Cr3 + using electro-synthesized poly(N-(9-fluorenylmethoxycarbonyl)-l-histidine)

Hui Zhang,Ge Zhang,Jingkun Xu,Yangping Wen,Shouli Ming,Jie Zhang,Wanchuan Ding

Trivalent chromium (Cr 3   + ) can cause severely environment pollution, declining quality of edible agro-products in plants and animals, and human diseases. Poly( N -(9-fluorenylmethoxycarbonyl)- l -histidine) (PFLH) synthesized by the direct electro-polymerization of its corresponding commercially available monomer in both boron trifluoride diethyl etherate and dichloromethane mixed system. The “turn-on” type fluorescent sensor based on PFLH displayed high sensitivity and selectivity for Cr 3   + detecting. The structure of PFLH was rationally proved by 1 H NMR spectra, FT-IR spectra, quantum chemical calculations , and its optical properties were characterized. The electro-synthesized PFLH exhibited a “turn-on” fluorescent response towards Cr 3   + , which was employed as a sensing platform for the “turn-on” fluorescent analysis of Cr 3   + in a wide linear range from 5.1   nM to 25   μM with a low limit of detection as low as 1.7   nM. The possible mechanism of fluorescent “turn-on” sensor based on PFLH for Cr 3   + was proposed. The sensor displayed high sensitivity, good selectivity, satisfactory practicability, suggesting that PFLH has potential fluorescent application for “turn-on” sensing Cr 3   + in agricultural environments and edible agro-products of plants and animals.

研究领域: 环境科学 · 分析化学
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Acta Biomaterialia · 2017 · IF 6.319

Unsaturated nitrogen-rich polymer poly(l-histidine) gated reversibly switchable mesoporous silica nanoparticles using “graft to” strategy for drug controlled release

Shengjun Mu,Yongjun Liu,Tianqi Wang,Jing Zhang,Dandan Jiang,Xiaoyue Yu,Na Zhang

A novel and intelligent pH-controlled system having an “on-off” switch based on poly( l -histidine) (PLH) and poly(ethylene glycol) (PEG) coated mesoporous silica nanoparticles (MSNs) (MSNs-PLH-PEG) was designed and evaluated for tumor specific drug release. The unsaturated nitrogen-rich polymer, PLH, which can change its solubility at different pH values, was employed for establishing the reversible “on-off” switch. In vitro drug release results demonstrated that MSNs-PLH-PEG has a pH-controlled “on-off” profile with the change of pH value between pH 7.4 and 5.0. Furthermore, in vitro cellular uptake study results showed that the entrapped drug could be efficiently released from MSNs-PLH-PEG under acidic endosome/lysosome. In vitro cell cytotoxicity and in vivo antitumor studies results indicated that sorafenib loaded MSNs-PLH-PEG exhibited good anti-proliferation and tumor growth inhibition effects. Haemolysis assay and histological analysis of MSNs-PLH-PEG showed negligible haemolysis activity and no visible tissue toxicity at the test dose. This study represents a promising and intelligent pH-controlled intelligent system for drug delivery and controlled release. Statement of Significance A novel pH-controlled intelligent and reversible “on-off” switch system based on poly( l -histidine) and poly(ethylene glycol) coated mesoporous silica nanoparticles (MSNs-PLH-PEG) by “graft to” synthesis method was constructed for tumor specific drug release. The unsaturated nitrogen-rich pH-sensitive polymer, PLH, which can change its solubility in different pH values, was employed as the reversible “on-off” switch in MSNs for the first time. The pH-controlled “on-off” switch manner was observed in the drug release results in vitro . In the in vivo antitumor studies, sorafenib loaded MSNs-PLH-PEG could effectively suppressed tumor growth in H22 tumor bearing mice. It is expected that the pH-controlled intelligent “on-off” switch system we designed holds remarkable promise and provides valuable strategy for possible applications in cancer therapy.

研究领域: 药学 · 生物材料 · 肿瘤学
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Analytical Methods · 2025 · IF 2.6

Separation of dithiothreitol and dithioerythritol by an open tubular capillary electrochromatographic column with a MOF modified by histidine as stationary phase

Mo Chen,lidi Gao,Huiying Liu,Jiawen Yu,Fuquan Zhao,Ming Li Bai,Hongtao Chu,Ming Zhao,Shili Qin

A separation and determination method of dithiothreitol (DTT), as an important small molecule reducing agent, and dithioerythritol (DTE), as a C3-epimer of DTT, was developed by capillary electrochromatography. A functional MOF (His-ZIF-93) was first prepared by using ZIF-93 (synthesized via coordination between 4-methylimidazole-5-carbaldehyde and Zn2+) as the framework and D-histidine (D-His) as a modifier, and then was bonded to the inner wall of the capillary column to obtain His-ZIF-93 column by Schiff base reaction. The results showed that the baseline separation of DTT and DTE was easily obtained under a very wide experimental conditions with a extremely short analysis time with less than 3 min. Separation mechanism was proved by the binding constant experiments. There was a good linearity between concentration (0.10-5.0 mg/mL) and peak area of DTT and DTE (R2 ≥ 0.996), and the relative standard deviations for the peak area and the retention time were less than 0.93%. The average impurity content of DTE in a 5.0 mg/mL DTT were 0.79%. Thus, the method was able to realize for the simple and fast separation and precise quantification of DTT and DTE.

CAS / MDL: 68282-53-1 62-56-6
研究领域: 分析化学 · 生物化学
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ACS Sustainable Chemistry & Engineering · 2026 · IF 7.6

Histidine-Grafted Polyamide Nanofiltration Membranes with Enhanced Acid Resistance and Electro-Nanofiltration for Lithium Separation from Acidic Lithium-Ion Battery Leachates

Wang Yuwei,Hui Boyang,Wang Hong,Liu Jinjin,Song Yunfei,He Benqiao

The recovery of lithium from spent lithium-ion battery (LIB) leachates remained challenging because strong acidity and complex ion compositions compromised the stability and selectivity of conventional nanofiltration (NF) membranes. In this work, an acid-resistant membrane was synthesized via covalent grafting of histidine (HIS) onto a polyamide (PA) layer (PA-HIS) through secondary interfacial polymerization (IP). In acidic media, imidazole protonation generated positively charged imidazolium sites that repelled H + , suppressing acid-catalyzed amide hydrolysis. Beyond this protective effect, HIS moieties enhanced surface hydration and water flux. The imidazole groups further promoted multivalent cation coordination and improved ion selectivity. This modified membrane maintained 98.9% Na 2 SO 4 rejection after 28 days at pH = 1, demonstrating excellent chemical durability. When electro-nanofiltration (ENF) based on the PA-HIS membrane was carried out for separating simulated acidic LIB leachates, the rejection of Ni 2+ , Co 2+ , and Mn 2+ of over 99.8% and Li + rejection of –35% were achieved to yield a separation factor S Li/(Ni,Co,Mn) of around 600. Continuous operational stability was further confirmed and exhibited exceptionally high ion selectivity ( S Li/(Ni,Co,Mn) > 400). These results demonstrated that HIS grafting enhanced acid durability, and electric field regulated ion discrimination, facilitating Li recovery from acidic LIB leachates.

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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS · 2025 · IF 4.3

Mechanistic insights into PS80 oxidative degradation in glass vials: Roles of critical factors (iron, histidine, aluminum, zinc) and their synergistic interactions

Zhuan Cheng,Pengzhen Wang,Xu Gao,Luting Liu,Quanmin Chen,Jeremy Guo

Polysorbate 80 (PS80), a vital stabilizer in biotherapeutic formulations, faces persistent oxidative degradation challenges that threaten drug product stability during storage. While PS80 instability has been studied for decades, the oxidation mechanisms in specific formulation-packaging systems remain poorly understood. This work resolves this knowledge gap by demonstrating that PS80 oxidative degradation occurs exclusively in histidine-buffered formulations stored in glass vials. This phenomenon was found to be driven by four factors: iron (leaching from vials promoted by histidine), histidine, zinc (histidine-introduced) and aluminum (glass-derived). These four interdependent factors exhibited a unique functional synergy: 1) iron as the radical chain initiator; 2) histidine as a pro-oxidative cofactor lowering iron’s catalytic threshold via formation of an iron-histidine complex; 3) zinc and aluminum accelerate Fe 2+ /Fe 3+ redox cycling through distinct potential-specific mechanisms, enhancing the overall catalytic efficiency. This study for the first time provides the systematic evidence of the histidine-glass system as an essential prerequisite for PS80 oxidation and reveals novel mechanistic insights on the interplay between formulation composition and packaging-derived contaminants. The findings establish a predictive framework to mitigate PS80 oxidative degradation, ultimately enhancing the stability and safety of protein therapeutics.

CAS / MDL: 7646-85-7
研究领域: 药学 · 生物化学 · 材料科学 · 分析化学 · 生物技术
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